6-82364969-G-C

Variant names:

• chr6-82364969-G-C
• rs1283207806
• NM_001376922.1:c.8G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376922.1(TPBG):​c.8G>C​(p.Gly3Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TPBG NM_001376922.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08270559).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376922.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPBG	NM_001376922.1	MANE Select	c.8G>C	p.Gly3Ala	missense	Exon 2 of 2	NP_001363851.1	Q13641
	TPBG	NM_001166392.2		c.8G>C	p.Gly3Ala	missense	Exon 2 of 2	NP_001159864.1	Q13641
	TPBG	NM_006670.5		c.8G>C	p.Gly3Ala	missense	Exon 3 of 3	NP_006661.1	Q13641

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPBG	ENST00000369750.4	TSL:1 MANE Select	c.8G>C	p.Gly3Ala	missense	Exon 2 of 2	ENSP00000358765.4	Q13641
	TPBG	ENST00000535040.4	TSL:2	c.8G>C	p.Gly3Ala	missense	Exon 3 of 3	ENSP00000441219.1	Q13641
	TPBG	ENST00000543496.3	TSL:2	c.8G>C	p.Gly3Ala	missense	Exon 2 of 2	ENSP00000440049.1	Q13641

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355558 Hom.: 0 Cov.: 30 AF XY: 0.00000150 AC XY: 1 AN XY: 666416

African (AFR) AF: 0.00 AC: 0 AN: 28436

American (AMR) AF: 0.00 AC: 0 AN: 31020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21916

East Asian (EAS) AF: 0.00 AC: 0 AN: 32492

South Asian (SAS) AF: 0.00 AC: 0 AN: 71118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4378

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1062838

Other (OTH) AF: 0.00 AC: 0 AN: 55988

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.36	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.38
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.057
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.43	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.21		Gain of glycosylation at S6 (P = 0.212)
MVP		0.53
MPC		1.6
ClinPred		0.68	D
GERP RS		1.3
Varity_R		0.19
gMVP		0.39
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1283207806; hg19: chr6-83074686;