chr6-82365309-GCTGGCGGAGCTGGCCGCGCTCAAC-G

Position:

• chr6-82365309-GCTGGCGGAGCTGGCCGCGCTCAAC-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000369750.4(TPBG):​c.351_374del​(p.Ala118_Leu125del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPBG ENST00000369750.4 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000369750.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPBG	NM_001376922.1	c.351_374del	p.Ala118_Leu125del	inframe_deletion	2/2	ENST00000369750.4	NP_001363851.1
TPBG	NM_001166392.2	c.351_374del	p.Ala118_Leu125del	inframe_deletion	2/2		NP_001159864.1
TPBG	NM_006670.5	c.351_374del	p.Ala118_Leu125del	inframe_deletion	3/3		NP_006661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPBG	ENST00000369750.4	c.351_374del	p.Ala118_Leu125del	inframe_deletion	2/2	1	NM_001376922.1	ENSP00000358765	P1
TPBG	ENST00000535040.4	c.351_374del	p.Ala118_Leu125del	inframe_deletion	3/3	2		ENSP00000441219	P1
TPBG	ENST00000543496.3	c.351_374del	p.Ala118_Leu125del	inframe_deletion	2/2	2		ENSP00000440049	P1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Apr 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-83075026;