chr15-39581891-C-G

Variant names:

• chr15-39581891-C-G
• NM_003246.4:c.34C>G

Variant summary

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

The NM_003246.4(THBS1):​c.34C>G​(p.Leu12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: THBS1 NM_003246.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

Genes affected

THBS1 (HGNC:11785): (thrombospondin 1) The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. [provided by RefSeq, Jul 2008]

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=0.16925573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS1	NM_003246.4	c.34C>G	p.Leu12Val	missense_variant	Exon 2 of 22	ENST00000260356.6	NP_003237.2
THBS1	XM_047432980.1	c.34C>G	p.Leu12Val	missense_variant	Exon 2 of 22		XP_047288936.1
THBS1	XM_011521971.3	c.34C>G	p.Leu12Val	missense_variant	Exon 2 of 21		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356.6	c.34C>G	p.Leu12Val	missense_variant	Exon 2 of 22	1	NM_003246.4	ENSP00000260356.5
THBS1	ENST00000397591.2	c.34C>G	p.Leu12Val	missense_variant	Exon 2 of 3	2		ENSP00000380720.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.019
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.76	N;N
REVEL	Benign	0.096
Sift	Benign	0.031	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.15	.;B
Vest4		0.46
MutPred		0.33		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.66
MPC		0.44
ClinPred		0.49	T
GERP RS		4.0
Varity_R		0.10
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-39874092;