Variant 6-82365082-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000369750.4(TPBG):c.121T>G(p.Phe41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TPBG
ENST00000369750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

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 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=0.079589486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TPBG	NM_001376922.1 linkuse as main transcript	c.121T>G	p.Phe41Val	missense_variant	2/2	ENST00000369750.4	NP_001363851.1
TPBG	NM_001166392.2 linkuse as main transcript	c.121T>G	p.Phe41Val	missense_variant	2/2		NP_001159864.1
TPBG	NM_006670.5 linkuse as main transcript	c.121T>G	p.Phe41Val	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.121T>G	p.Phe41Val	missense_variant	2/2	1	NM_001376922.1	ENSP00000358765	P1
TPBG	ENST00000535040.4 linkuse as main transcript	c.121T>G	p.Phe41Val	missense_variant	3/3	2		ENSP00000441219	P1
TPBG	ENST00000543496.3 linkuse as main transcript	c.121T>G	p.Phe41Val	missense_variant	2/2	2		ENSP00000440049	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412396

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698414

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.121T>G (p.F41V) alteration is located in exon 3 (coding exon 1) of the TPBG gene. This alteration results from a T to G substitution at nucleotide position 121, causing the phenylalanine (F) at amino acid position 41 to be replaced by a valine (V). 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

0.072

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.060

M_CAP

Benign

0.046

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.19

N;N;N

REVEL

Benign

0.073

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.075

MutPred

0.20

Gain of glycosylation at P46 (P = 0.1265);Gain of glycosylation at P46 (P = 0.1265);Gain of glycosylation at P46 (P = 0.1265);

MVP

0.52

MPC

0.82

ClinPred

0.086

GERP RS

3.1

Varity_R

0.080

gMVP

0.36

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