Genetic Variant THSD7B:p.Arg127Gly (chr2-137056659-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001316349.2(THSD7B):c.379C>G(p.Arg127Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

THSD7B
NM_001316349.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

Variant links:

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]

THSD7B links:

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ACMG classification

Classification made for transcript

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=0.24079323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7B	NM_001316349.2 link	c.379C>G	p.Arg127Gly	missense_variant	Exon 3 of 28	ENST00000409968.6	NP_001303278.1	Q9C0I4
THSD7B	XM_047445935.1 link	c.-45C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 28		XP_047301891.1
THSD7B	XM_047445935.1 link	c.-45C>G		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 link	c.379C>G	p.Arg127Gly	missense_variant	Exon 3 of 28	5	NM_001316349.2	ENSP00000387145.1		Q9C0I4
THSD7B	ENST00000472720.5 link	n.*345C>G		downstream_gene_variant		5		ENSP00000473349.1		R4GMU2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249034

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286C>G (p.R96G) alteration is located in exon 2 (coding exon 2) of the THSD7B gene. This alteration results from a C to G substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a glycine (G). 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

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

T;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.64

T;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.86

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.079

Sift

Uncertain

0.0090

D;D;D

Sift4G

Benign

0.23

T;T;T

Polyphen

1.0

.;.;D

Vest4

0.21

MutPred

0.48

.;.;Gain of catalytic residue at R96 (P = 0.0551);

MVP

0.55

MPC

0.61

ClinPred

0.87

GERP RS

1.0

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over