rs148939821

Variant names:

• chr7-11406947-C-G
• rs148939821
• NM_015204.3:c.4025G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-11406947-C-G
• chr7-11406947-C-T

Variant summary

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

The NM_015204.3(THSD7A):​c.4025G>C​(p.Arg1342Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THSD7A NM_015204.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=0.25668466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.4025G>C	p.Arg1342Pro	missense_variant	Exon 21 of 28	ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.4025G>C	p.Arg1342Pro	missense_variant	Exon 21 of 28	5	NM_015204.3	ENSP00000406482.2
ENSG00000230333	ENST00000445839.5	n.441+23039C>G		intron_variant	Intron 3 of 3	4
ENSG00000230435	ENST00000425837.1	n.-8C>G		upstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461564 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727054

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.15
Sift	Benign	0.077	T;.
Sift4G	Benign	0.086	T;T
Polyphen		0.18	B;.
Vest4		0.71
MutPred		0.42		Gain of ubiquitination at K1338 (P = 0.0439);Gain of ubiquitination at K1338 (P = 0.0439);
MVP		0.15
MPC		0.10
ClinPred		0.26	T
GERP RS		-0.66
Varity_R		0.24
gMVP		0.63

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

Other links and lift over

dbSNP: rs148939821; hg19: chr7-11446574;