2-137231118-A-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.1798A>T(p.Met600Leu) 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. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: THSD7B NM_001316349.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

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=0.122826904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7B	NM_001316349.2	c.1798A>T	p.Met600Leu	missense_variant	8/28	ENST00000409968.6
THSD7B	XM_047445935.1	c.1375A>T	p.Met459Leu	missense_variant	8/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7B	ENST00000409968.6	c.1798A>T	p.Met600Leu	missense_variant	8/28	5	NM_001316349.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 14, 2022

The c.1705A>T (p.M569L) alteration is located in exon 7 (coding exon 7) of the THSD7B gene. This alteration results from a A to T substitution at nucleotide position 1705, causing the methionine (M) at amino acid position 569 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	18
Dann	Benign	0.95
DEOGEN2	Benign	0.016	T;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.69	T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.082
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.29	.;.;B
Vest4		0.26
MutPred		0.29		Loss of catalytic residue at M600 (P = 0.0056);Loss of catalytic residue at M600 (P = 0.0056);.;
MVP		0.42
MPC		0.16
ClinPred		0.56	D
GERP RS		4.7
gMVP		0.22

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: chr2-137988688;