Variant 7-11376588-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015204.3(THSD7A):c.4871C>G(p.Ser1624Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,583,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

THSD7A
NM_015204.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52

Variant links:

Genes affected

THSD7A (HGNC:22207): (thrombospondin type 1 domain containing 7A) The protein encoded by this gene is found almost exclusively in endothelial cells from placenta and umbilical cord. The encoded protein appears to interact with alpha(V)beta(3) integrin and paxillin to inhibit endothelial cell migration and tube formation. This protein may be involved in cytoskeletal organization. Variations in this gene may be associated with low bone mineral density in osteoporosis. [provided by RefSeq, Aug 2010]

THSD7A links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18788591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3 linkuse as main transcript	c.4871C>G	p.Ser1624Cys	missense_variant	27/28	ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9 linkuse as main transcript	c.4871C>G	p.Ser1624Cys	missense_variant	27/28	5	NM_015204.3	P1
	ENST00000445839.5 linkuse as main transcript	n.247-2699G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000772

AC:

AN:

207324

Hom.:

AF XY:

0.0000451

AC XY:

AN XY:

110748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000525

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000161

AC:

AN:

1430990

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

708700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000486

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000118

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000227

ExAC

AF:

0.0000250

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.4871C>G (p.S1624C) alteration is located in exon 27 (coding exon 27) of the THSD7A gene. This alteration results from a C to G substitution at nucleotide position 4871, causing the serine (S) at amino acid position 1624 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.95

N;.

REVEL

Uncertain

0.35

Sift

Benign

0.18

T;.

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;.

Vest4

0.70

MutPred

0.42

Loss of MoRF binding (P = 0.0806);Loss of MoRF binding (P = 0.0806);

MVP

0.22

MPC

0.19

ClinPred

0.35

GERP RS

5.1

Varity_R

0.27

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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