2-137056491-G-T

Variant names:

• chr2-137056491-G-T
• NM_001316349.2:c.211G>T

Variant summary

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

The NM_001316349.2(THSD7B):​c.211G>T​(p.Val71Phe) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THSD7B NM_001316349.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.135

Genes affected

THSD7B (HGNC:29348): (thrombospondin type 1 domain containing 7B) Predicted to be involved in actin cytoskeleton reorganization. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10998878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7B	NM_001316349.2	c.211G>T	p.Val71Phe	missense_variant	Exon 3 of 28	ENST00000409968.6	NP_001303278.1
THSD7B	XM_047445935.1	c.-213G>T		5_prime_UTR_variant	Exon 3 of 28		XP_047301891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7B	ENST00000409968.6	c.211G>T	p.Val71Phe	missense_variant	Exon 3 of 28	5	NM_001316349.2	ENSP00000387145.1
THSD7B	ENST00000472720.5	n.*177G>T		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000473349.1
THSD7B	ENST00000472720.5	n.*177G>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000473349.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.118G>T (p.V40F) alteration is located in exon 2 (coding exon 2) of the THSD7B gene. This alteration results from a G to T substitution at nucleotide position 118, causing the valine (V) at amino acid position 40 to be replaced by a phenylalanine (F). 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	0.079
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.83	T;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.048	D;D;T
Sift4G	Benign	0.071	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.22
MutPred		0.40		.;.;Gain of catalytic residue at V40 (P = 0.1238);
MVP		0.55
MPC		0.46
ClinPred		0.085	T
GERP RS		-0.29
gMVP		0.37

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: chr2-137814061;