Variant 6-82365580-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000369750.4(TPBG):c.619C>G(p.Arg207Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TPBG
ENST00000369750.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.364

Variant links:

Genes affected

TPBG (HGNC:12004): (trophoblast glycoprotein) This gene encodes a leucine-rich transmembrane glycoprotein that may be involved in cell adhesion. The encoded protein is an oncofetal antigen that is specific to trophoblast cells. In adults this protein is highly expressed in many tumor cells and is associated with poor clinical outcome in numerous cancers. Alternate splicing in the 5' UTR results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2009]

TPBG links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06731182).

BP6

Variant 6-82365580-C-G is Benign according to our data. Variant chr6-82365580-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3328251.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TPBG	NM_001376922.1 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	2/2	ENST00000369750.4	NP_001363851.1
TPBG	NM_001166392.2 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	2/2		NP_001159864.1
TPBG	NM_006670.5 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	3/3		NP_006661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TPBG	ENST00000369750.4 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	2/2	1	NM_001376922.1	ENSP00000358765	P1
TPBG	ENST00000535040.4 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	3/3	2		ENSP00000441219	P1
TPBG	ENST00000543496.3 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	2/2	2		ENSP00000440049	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

228728

Hom.:

AF XY:

0.00000812

AC XY:

AN XY:

123082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1438254

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.99

DANN

Benign

0.58

DEOGEN2

Benign

0.053

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.026

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.20

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.069

MutPred

0.55

Gain of catalytic residue at R207 (P = 0.0147);Gain of catalytic residue at R207 (P = 0.0147);Gain of catalytic residue at R207 (P = 0.0147);

MVP

0.54

MPC

0.80

ClinPred

0.029

GERP RS

2.0

Varity_R

0.39

gMVP

0.33

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