chr6-82365089-C-A

Variant names:

• chr6-82365089-C-A
• rs984020597
• NM_001376922.1:c.128C>A

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.128C>A​(p.Ser43Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TPBG NM_001376922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 1 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=0.15284434).

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.128C>A	p.Ser43Tyr	missense	Exon 2 of 2	NP_001363851.1	Q13641
	TPBG	NM_001166392.2		c.128C>A	p.Ser43Tyr	missense	Exon 2 of 2	NP_001159864.1	Q13641
	TPBG	NM_006670.5		c.128C>A	p.Ser43Tyr	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.128C>A	p.Ser43Tyr	missense	Exon 2 of 2	ENSP00000358765.4	Q13641
	TPBG	ENST00000535040.4	TSL:2	c.128C>A	p.Ser43Tyr	missense	Exon 3 of 3	ENSP00000441219.1	Q13641
	TPBG	ENST00000543496.3	TSL:2	c.128C>A	p.Ser43Tyr	missense	Exon 2 of 2	ENSP00000440049.1	Q13641

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.12
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.62	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.15
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.023	D
Polyphen		0.28	B
Vest4		0.23
MutPred		0.27		Loss of glycosylation at S43 (P = 0.0081)
MVP		0.63
MPC		0.85
ClinPred		0.15	T
GERP RS		2.9
Varity_R		0.075
gMVP		0.39
Mutation Taster		=95/5	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: rs984020597; hg19: chr6-83074806;