Variant 13-52377667-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_018676.4(THSD1):c.2303A>G(p.Lys768Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,610,070 control chromosomes in the GnomAD database, including 2,000 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.039 ( 136 hom., cov: 33)

Exomes 𝑓: 0.048 ( 1864 hom. )

Consequence

THSD1
NM_018676.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.61

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014523864).

BP6

Variant 13-52377667-T-C is Benign according to our data. Variant chr13-52377667-T-C is described in ClinVar as [Benign]. Clinvar id is 3037862.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD1	NM_018676.4 linkuse as main transcript	c.2303A>G	p.Lys768Arg	missense_variant	5/5	ENST00000258613.5	NP_061146.1
THSD1	NM_199263.3 linkuse as main transcript	c.2144A>G	p.Lys715Arg	missense_variant	4/4		NP_954872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD1	ENST00000258613.5 linkuse as main transcript	c.2303A>G	p.Lys768Arg	missense_variant	5/5	1	NM_018676.4	ENSP00000258613	P1	Q9NS62-1
THSD1	ENST00000349258.8 linkuse as main transcript	c.2144A>G	p.Lys715Arg	missense_variant	4/4	1		ENSP00000340650		Q9NS62-2
THSD1	ENST00000648254.1 linkuse as main transcript	c.2144A>G	p.Lys715Arg	missense_variant	4/4			ENSP00000497520		Q9NS62-2

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5903

AN:

152180

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.0606

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.0687

Gnomad FIN

AF:

0.0394

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0491

Gnomad OTH

AF:

0.0436

GnomAD3 exomes

AF:

0.0429

AC:

10758

AN:

250486

Hom.:

294

AF XY:

0.0464

AC XY:

6282

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.0219

Gnomad ASJ exome

AF:

0.0705

Gnomad EAS exome

AF:

0.00799

Gnomad SAS exome

AF:

0.0642

Gnomad FIN exome

AF:

0.0422

Gnomad NFE exome

AF:

0.0496

Gnomad OTH exome

AF:

0.0467

GnomAD4 exome

AF:

0.0478

AC:

69627

AN:

1457772

Hom.:

1864

Cov.:

AF XY:

0.0485

AC XY:

35166

AN XY:

724344

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.0219

Gnomad4 ASJ exome

AF:

0.0656

Gnomad4 EAS exome

AF:

0.00771

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.0419

Gnomad4 NFE exome

AF:

0.0494

Gnomad4 OTH exome

AF:

0.0479

GnomAD4 genome

AF:

0.0388

AC:

5909

AN:

152298

Hom.:

136

Cov.:

AF XY:

0.0385

AC XY:

2865

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.0305

Gnomad4 ASJ

AF:

0.0606

Gnomad4 EAS

AF:

0.00849

Gnomad4 SAS

AF:

0.0690

Gnomad4 FIN

AF:

0.0394

Gnomad4 NFE

AF:

0.0491

Gnomad4 OTH

AF:

0.0479

Alfa

AF:

0.0464

Hom.:

411

Bravo

AF:

0.0364

TwinsUK

AF:

0.0445

AC:

165

ALSPAC

AF:

0.0501

AC:

193

ESP6500AA

AF:

0.0270

AC:

119

ESP6500EA

AF:

0.0509

AC:

438

ExAC

AF:

0.0441

AC:

5353

Asia WGS

AF:

0.0530

AC:

186

AN:

3478

EpiCase

AF:

0.0524

EpiControl

AF:

0.0538

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

THSD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 23, 2024

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

0.061

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.29

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.67

.;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.96

.;N;.

MutationTaster

Benign

0.90

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.28

N;N;.

REVEL

Benign

0.092

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.047

MPC

0.20

ClinPred

0.0025

GERP RS

2.7

Varity_R

0.028

gMVP

0.097

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over