NM_003246.4:c.121C>T

Variant names:

• chr15-39582246-C-T
• NM_003246.4:c.121C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003246.4(THBS1):​c.121C>T​(p.Arg41Cys) 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 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THBS1 NM_003246.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41496515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS1	NM_003246.4	c.121C>T	p.Arg41Cys	missense_variant	Exon 3 of 22	ENST00000260356.6	NP_003237.2
THBS1	XM_047432980.1	c.121C>T	p.Arg41Cys	missense_variant	Exon 3 of 22		XP_047288936.1
THBS1	XM_011521971.3	c.121C>T	p.Arg41Cys	missense_variant	Exon 3 of 21		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356.6	c.121C>T	p.Arg41Cys	missense_variant	Exon 3 of 22	1	NM_003246.4	ENSP00000260356.5
THBS1	ENST00000397591.2	c.121C>T	p.Arg41Cys	missense_variant	Exon 3 of 3	2		ENSP00000380720.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461642 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727114

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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	.;D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.9	D;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.96	.;D
Vest4		0.56
MutPred		0.45		Loss of disorder (P = 0.0173);Loss of disorder (P = 0.0173);
MVP		0.34
MPC		1.2
ClinPred		0.98	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.78

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: chr15-39874447;