6-82365685-A-G

Variant names:

• chr6-82365685-A-G
• rs377740252
• NM_001376922.1:c.724A>G

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.724A>G​(p.Ser242Gly) 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. 17/22 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: TPBG NM_001376922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.555
• 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=0.12221214).

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.724A>G	p.Ser242Gly	missense	Exon 2 of 2	NP_001363851.1	Q13641
	TPBG	NM_001166392.2		c.724A>G	p.Ser242Gly	missense	Exon 2 of 2	NP_001159864.1	Q13641
	TPBG	NM_006670.5		c.724A>G	p.Ser242Gly	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.724A>G	p.Ser242Gly	missense	Exon 2 of 2	ENSP00000358765.4	Q13641
	TPBG	ENST00000535040.4	TSL:2	c.724A>G	p.Ser242Gly	missense	Exon 3 of 3	ENSP00000441219.1	Q13641
	TPBG	ENST00000543496.3	TSL:2	c.724A>G	p.Ser242Gly	missense	Exon 2 of 2	ENSP00000440049.1	Q13641

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.75
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.56
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.36	T
Sift4G	Benign	0.41	T
Polyphen		0.0070	B
Vest4		0.11
MVP		0.59
MPC		0.58
ClinPred		0.034	T
GERP RS		4.0
Varity_R		0.22
gMVP		0.58
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs377740252; hg19: chr6-83075402;