Genetic Variant TPBG:p.Leu65Pro (chr6-82365155-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001376922.1(TPBG):c.194T>C(p.Leu65Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TPBG
NM_001376922.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.583

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13576803).

BP6

Variant 6-82365155-T-C is Benign according to our data. Variant chr6-82365155-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3809740.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPBG	NM_001376922.1	MANE Select	c.194T>C	p.Leu65Pro	missense	Exon 2 of 2	NP_001363851.1	Q13641
TPBG	NM_001166392.2		c.194T>C	p.Leu65Pro	missense	Exon 2 of 2	NP_001159864.1	Q13641
TPBG	NM_006670.5		c.194T>C	p.Leu65Pro	missense	Exon 3 of 3	NP_006661.1	Q13641

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPBG	ENST00000369750.4	TSL:1 MANE Select	c.194T>C	p.Leu65Pro	missense	Exon 2 of 2	ENSP00000358765.4	Q13641
TPBG	ENST00000535040.4	TSL:2	c.194T>C	p.Leu65Pro	missense	Exon 3 of 3	ENSP00000441219.1	Q13641
TPBG	ENST00000543496.3	TSL:2	c.194T>C	p.Leu65Pro	missense	Exon 2 of 2	ENSP00000440049.1	Q13641

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000129

AC:

AN:

231800

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000614

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000959

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722756

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32448

American (AMR)

AF:

0.0000456

AC:

AN:

43822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25732

East Asian (EAS)

AF:

0.00

AC:

AN:

38718

South Asian (SAS)

AF:

0.00

AC:

AN:

85150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108864

Other (OTH)

AF:

0.00

AC:

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.036

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

8.9

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.34

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.66

MutationAssessor

Benign

-1.3

PhyloP100

-0.58

PrimateAI

Benign

0.41

PROVEAN

Benign

1.0

REVEL

Benign

0.18

Sift

Benign

0.30

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.097

MutPred

0.45

Gain of disorder (P = 0.0296)

MVP

0.19

MPC

1.0

ClinPred

0.060

GERP RS

0.067

Varity_R

0.20

gMVP

0.59

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over