13-52378061-C-A

Position:

• chr13-52378061-C-A

Variant summary

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

The NM_018676.4(THSD1):​c.1909G>T​(p.Gly637Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THSD1 NM_018676.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91

Genes affected

THSD1 (HGNC:17754): (thrombospondin type 1 domain containing 1) The protein encoded by this gene contains a type 1 thrombospondin domain, which is found in a number of proteins involved in the complement pathway, as well as in extracellular matrix proteins. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jan 2009]

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=0.30376524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD1	NM_018676.4	c.1909G>T	p.Gly637Trp	missense_variant	5/5	ENST00000258613.5	NP_061146.1
THSD1	NM_199263.3	c.1750G>T	p.Gly584Trp	missense_variant	4/4		NP_954872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD1	ENST00000258613.5	c.1909G>T	p.Gly637Trp	missense_variant	5/5	1	NM_018676.4	ENSP00000258613	P1
THSD1	ENST00000349258.8	c.1750G>T	p.Gly584Trp	missense_variant	4/4	1		ENSP00000340650
THSD1	ENST00000648254.1	c.1750G>T	p.Gly584Trp	missense_variant	4/4			ENSP00000497520

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Mar 16, 2024

The c.1909G>T (p.G637W) alteration is located in exon 5 (coding exon 4) of the THSD1 gene. This alteration results from a G to T substitution at nucleotide position 1909, causing the glycine (G) at amino acid position 637 to be replaced by a tryptophan (W). 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	0.22
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	.;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.6	.;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.8	D;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.017	D;D;.
Sift4G	Uncertain	0.014	D;D;.
Polyphen		1.0	D;D;D
Vest4		0.48
MutPred		0.20		.;Loss of methylation at R636 (P = 0.0201);.;
MVP		0.14
MPC		0.96
ClinPred		0.93	D
GERP RS		5.3
Varity_R		0.091
gMVP		0.26

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: chr13-52952196;