Variant 7-11379138-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015204.3(THSD7A):c.4733A>C(p.His1578Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

THSD7A
NM_015204.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

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:

THSD7A (HGNC:):

THSD7A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3139248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD7A	NM_015204.3 linkuse as main transcript	c.4733A>C	p.His1578Pro	missense_variant	26/28	ENST00000423059.9	NP_056019.1	Q9UPZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9 linkuse as main transcript	c.4733A>C	p.His1578Pro	missense_variant	26/28	5	NM_015204.3	ENSP00000406482.2		Q9UPZ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248932

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

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:

0.00000274

AC:

AN:

1461378

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Aug 08, 2022

The c.4733A>C (p.H1578P) alteration is located in exon 26 (coding exon 26) of the THSD7A gene. This alteration results from a A to C substitution at nucleotide position 4733, causing the histidine (H) at amino acid position 1578 to be replaced by a proline (P). 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

0.094

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.060

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.84

N;.

REVEL

Benign

0.096

Sift

Benign

0.082

T;.

Sift4G

Uncertain

0.024

D;D

Polyphen

0.0

B;.

Vest4

0.63

MutPred

0.15

Gain of glycosylation at H1578 (P = 0.0317);Gain of glycosylation at H1578 (P = 0.0317);

MVP

0.043

MPC

0.12

ClinPred

0.38

GERP RS

6.1

Varity_R

0.28

gMVP

0.69

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