Genetic Variant THSD7A:p.Ala578Ala (chr7-11541507-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015204.3(THSD7A):c.1734A>G(p.Ala578Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,613,206 control chromosomes in the GnomAD database, including 150,358 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 14508 hom., cov: 32)

Exomes 𝑓: 0.43 ( 135850 hom. )

Consequence

THSD7A
NM_015204.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.467

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:

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 (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=0.467 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3 link	c.1734A>G	p.Ala578Ala	synonymous_variant	Exon 6 of 28	ENST00000423059.9	NP_056019.1	Q9UPZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9 link	c.1734A>G	p.Ala578Ala	synonymous_variant	Exon 6 of 28	5	NM_015204.3	ENSP00000406482.2		Q9UPZ6
THSD7A	ENST00000497575.1 link	n.223A>G		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66047

AN:

151798

Hom.:

14497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.394

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.425

AC:

105756

AN:

248892

Hom.:

22843

AF XY:

0.430

AC XY:

58102

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.505

Gnomad SAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.429

AC:

626991

AN:

1461290

Hom.:

135850

Cov.:

AF XY:

0.431

AC XY:

313608

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.484

Gnomad4 AMR exome

AF:

0.373

Gnomad4 ASJ exome

AF:

0.476

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.446

GnomAD4 genome

AF:

0.435

AC:

66092

AN:

151916

Hom.:

14508

Cov.:

AF XY:

0.433

AC XY:

32158

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.474

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.489

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.431

Hom.:

18223

Bravo

AF:

0.438

Asia WGS

AF:

0.458

AC:

1595

AN:

3478

EpiCase

AF:

0.430

EpiControl

AF:

0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

2.4

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over