7-11379650-G-A

Position:

• chr7-11379650-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015204.3(THSD7A):​c.4570C>T​(p.Pro1524Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,436,286 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: THSD7A NM_015204.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

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]

ENSG00000230333 (HGNC:):

ACMG classification

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=0.24955171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.4570C>T	p.Pro1524Ser	missense_variant	25/28	ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.4570C>T	p.Pro1524Ser	missense_variant	25/28	5	NM_015204.3	ENSP00000406482.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436286 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 711726

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: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.4570C>T (p.P1524S) alteration is located in exon 25 (coding exon 25) of the THSD7A gene. This alteration results from a C to T substitution at nucleotide position 4570, causing the proline (P) at amino acid position 1524 to be replaced by a serine (S). 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	0.081
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Benign	0.25
Sift	Uncertain	0.016	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	D;.
Vest4		0.24
MutPred		0.31		Gain of glycosylation at P1524 (P = 0.0441);Gain of glycosylation at P1524 (P = 0.0441);
MVP		0.093
MPC		0.072
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-11419277;