Variant 7-11406403-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015204.3(THSD7A):c.4134T>A(p.Asp1378Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,613,930 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

THSD7A
NM_015204.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.299

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032844245).

BP6

Variant 7-11406403-A-T is Benign according to our data. Variant chr7-11406403-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 722290.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3 linkuse as main transcript	c.4134T>A	p.Asp1378Glu	missense_variant	22/28	ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9 linkuse as main transcript	c.4134T>A	p.Asp1378Glu	missense_variant	22/28	5	NM_015204.3	P1
	ENST00000445839.5 linkuse as main transcript	n.441+22495A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.0000294

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000377

AC:

AN:

249020

Hom.:

AF XY:

0.000311

AC XY:

AN XY:

135086

show subpopulations

Gnomad AFR exome

AF:

0.00504

Gnomad AMR exome

AF:

0.000406

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:

0.00000886

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000145

AC:

212

AN:

1461636

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00460

Gnomad4 AMR exome

AF:

0.000537

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:

0.0000108

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152294

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000530

Hom.:

Bravo

AF:

0.00159

ESP6500AA

AF:

0.00283

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000389

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.86

N;.

REVEL

Benign

0.12

Sift

Benign

0.57

T;.

Sift4G

Benign

0.23

T;T

Polyphen

0.012

B;.

Vest4

0.34

MutPred

0.30

Gain of methylation at K1381 (P = 0.0801);Gain of methylation at K1381 (P = 0.0801);

MVP

0.068

MPC

0.26

ClinPred

0.016

GERP RS

1.1

Varity_R

0.083

gMVP

0.42

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