Variant 13-52397636-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PP3_StrongPP5_Moderate

The NM_018676.4(THSD1):c.617G>A(p.Cys206Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

THSD1
NM_018676.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 6.70

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 Likely_pathogenic. Variant got 6 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.95

PP5

Variant 13-52397636-C-T is Pathogenic according to our data. Variant chr13-52397636-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 190456.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD1	NM_018676.4 linkuse as main transcript	c.617G>A	p.Cys206Tyr	missense_variant	3/5	ENST00000258613.5	NP_061146.1
THSD1	NM_199263.3 linkuse as main transcript	c.617G>A	p.Cys206Tyr	missense_variant	3/4		NP_954872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD1	ENST00000258613.5 linkuse as main transcript	c.617G>A	p.Cys206Tyr	missense_variant	3/5	1	NM_018676.4	ENSP00000258613	P1	Q9NS62-1
THSD1	ENST00000349258.8 linkuse as main transcript	c.617G>A	p.Cys206Tyr	missense_variant	3/4	1		ENSP00000340650		Q9NS62-2
THSD1	ENST00000648254.1 linkuse as main transcript	c.617G>A	p.Cys206Tyr	missense_variant	3/4			ENSP00000497520		Q9NS62-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lymphatic malformation 13

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jun 03, 2015	- -
Likely pathogenic, criteria provided, single submitter	research	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Mar 17, 2024	- -

Non-immune hydrops fetalis

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Oct 30, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Uncertain

-0.040

MutationAssessor

Uncertain

2.7

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-11

D;D;.

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;D;D

Vest4

0.91

MutPred

0.78

Gain of phosphorylation at C206 (P = 0.0768);Gain of phosphorylation at C206 (P = 0.0768);Gain of phosphorylation at C206 (P = 0.0768);

MVP

0.85

MPC

1.2

ClinPred

1.0

GERP RS

5.5

Varity_R

0.91

gMVP

0.96

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