13-52397583-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_018676.4(THSD1):c.670C>G(p.Arg224Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 1,614,074 control chromosomes in the GnomAD database, including 2,340 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.058 ( 307 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2033 hom. )

Consequence

THSD1
NM_018676.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.710

Publications

14 publications found

Variant links:

Genes affected

THSD1 (HGNC:17754): (thrombospondin type 1 domain containing 1) The protein encoded by this gene contains a type 1 thrombospondin domain, which is found in a number of proteins involved in the complement pathway, as well as in extracellular matrix proteins. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jan 2009]

THSD1 Gene-Disease associations (from GenCC):

non-immune hydrops fetalis
Inheritance: AR Classification: DEFINITIVE Submitted by: King Faisal Specialist Hospital and Research Center
aneurysm, intracranial berry, 12
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
lymphatic malformation 13
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
intracranial berry aneurysm
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

THSD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014815629).

BP6

Variant 13-52397583-G-C is Benign according to our data. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-52397583-G-C is described in CliVar as Benign. Clinvar id is 3352968.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD1	NM_018676.4 link	c.670C>G	p.Arg224Gly	missense_variant	Exon 3 of 5	ENST00000258613.5	NP_061146.1	Q9NS62-1A0A024R064B3KTY7
THSD1	NM_199263.3 link	c.670C>G	p.Arg224Gly	missense_variant	Exon 3 of 4		NP_954872.1	Q9NS62-2B3KTY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
THSD1	ENST00000258613.5 link	c.670C>G	p.Arg224Gly	missense_variant	Exon 3 of 5	1	NM_018676.4	ENSP00000258613.4	Q9NS62-1
THSD1	ENST00000349258.8 link	c.670C>G	p.Arg224Gly	missense_variant	Exon 3 of 4	1		ENSP00000340650.4	Q9NS62-2
THSD1	ENST00000648254.1 link	c.670C>G	p.Arg224Gly	missense_variant	Exon 3 of 4			ENSP00000497520.1	Q9NS62-2

Frequencies

GnomAD3 genomes

AF:

0.0581

AC:

8845

AN:

152108

Hom.:

302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.00889

Gnomad SAS

AF:

0.0694

Gnomad FIN

AF:

0.0391

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0536

GnomAD2 exomes

AF:

0.0482

AC:

12115

AN:

251268

AF XY:

0.0503

show subpopulations

Gnomad AFR exome

AF:

0.0915

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0708

Gnomad EAS exome

AF:

0.00799

Gnomad FIN exome

AF:

0.0423

Gnomad NFE exome

AF:

0.0500

Gnomad OTH exome

AF:

0.0498

GnomAD4 exome

AF:

0.0498

AC:

72790

AN:

1461848

Hom.:

2033

Cov.:

AF XY:

0.0503

AC XY:

36592

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.0822

AC:

2752

AN:

33480

American (AMR)

AF:

0.0269

AC:

1203

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0662

AC:

1731

AN:

26136

East Asian (EAS)

AF:

0.00768

AC:

305

AN:

39700

South Asian (SAS)

AF:

0.0653

AC:

5636

AN:

86254

European-Finnish (FIN)

AF:

0.0419

AC:

2238

AN:

53416

Middle Eastern (MID)

AF:

0.0820

AC:

473

AN:

5768

European-Non Finnish (NFE)

AF:

0.0497

AC:

55241

AN:

1111978

Other (OTH)

AF:

0.0532

AC:

3211

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

4562

9124

13686

18248

22810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2106

4212

6318

8424

10530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0583

AC:

8871

AN:

152226

Hom.:

307

Cov.:

AF XY:

0.0572

AC XY:

4254

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0907

AC:

3766

AN:

41516

American (AMR)

AF:

0.0372

AC:

569

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0611

AC:

212

AN:

3468

East Asian (EAS)

AF:

0.00891

AC:

AN:

5162

South Asian (SAS)

AF:

0.0699

AC:

337

AN:

4822

European-Finnish (FIN)

AF:

0.0391

AC:

415

AN:

10604

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0496

AC:

3371

AN:

68032

Other (OTH)

AF:

0.0578

AC:

122

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

424

849

1273

1698

2122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0450

Hom.:

130

Bravo

AF:

0.0582

TwinsUK

AF:

0.0448

AC:

166

ALSPAC

AF:

0.0506

AC:

195

ESP6500AA

AF:

0.0858

AC:

378

ESP6500EA

AF:

0.0515

AC:

443

ExAC

AF:

0.0503

AC:

6113

Asia WGS

AF:

0.0590

AC:

204

AN:

3478

EpiCase

AF:

0.0525

EpiControl

AF:

0.0539

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

THSD1-related disorder

Benign:1

Jul 23, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0074

.;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.69

.;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;M

PhyloP100

0.71

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.051

Sift

Benign

0.16

T;T;.

Sift4G

Benign

0.23

T;T;.

Polyphen

0.71

P;B;P

Vest4

0.092

MPC

0.32

ClinPred

0.0043

GERP RS

2.5

Varity_R

0.053

gMVP

0.52

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over