Genetic Variant TMEM102:p.Pro358Leu (chr17-7437052-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178518.3(TMEM102):c.1073C>T(p.Pro358Leu) 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. 15/22 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM102
NM_178518.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.947

Publications

0 publications found

Variant links:

Genes affected

TMEM102 (HGNC:26722): (transmembrane protein 102) Involved in regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; response to cytokine; and signal transduction. Acts upstream of or within positive regulation of T cell migration and positive regulation of cell adhesion. Located in cell surface. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

TMEM102 links:

ENSG00000262624 (HGNC:):

ENSG00000262624 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=0.06077695).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178518.3. 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
	TMEM102	NM_178518.3	MANE Select	c.1073C>T	p.Pro358Leu	missense	Exon 3 of 3	NP_848613.1	Q8N9M5
	TMEM102	NM_001320444.1		c.1073C>T	p.Pro358Leu	missense	Exon 2 of 2	NP_001307373.1	Q8N9M5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM102	ENST00000323206.2	TSL:1 MANE Select	c.1073C>T	p.Pro358Leu	missense	Exon 3 of 3	ENSP00000315387.1	Q8N9M5
TMEM102	ENST00000396568.1	TSL:2	c.1073C>T	p.Pro358Leu	missense	Exon 2 of 2	ENSP00000379815.1	Q8N9M5
TMEM102	ENST00000860243.1		c.920C>T	p.Pro307Leu	missense	Exon 3 of 3	ENSP00000530302.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1412064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700506

African (AFR)

AF:

0.00

AC:

AN:

32516

American (AMR)

AF:

0.00

AC:

AN:

38196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25202

East Asian (EAS)

AF:

0.00

AC:

AN:

37834

South Asian (SAS)

AF:

0.00

AC:

AN:

82378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094740

Other (OTH)

AF:

0.00

AC:

AN:

58788

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.083

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.8

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.031

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.015

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

PhyloP100

-0.95

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

REVEL

Benign

0.012

Sift

Benign

0.12

Sift4G

Benign

0.070

Polyphen

0.044

Vest4

0.071

MutPred

0.36

Loss of glycosylation at P358 (P = 0.0479)

MVP

0.076

ClinPred

0.034

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.27

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over