Variant 17-7436991-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000323206.2(TMEM102):c.1012G>A(p.Gly338Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000691 in 1,447,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

TMEM102
ENST00000323206.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29182035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM102	NM_178518.3 linkuse as main transcript	c.1012G>A	p.Gly338Ser	missense_variant	3/3	ENST00000323206.2	NP_848613.1	Q8N9M5
TMEM102	NM_001320444.1 linkuse as main transcript	c.1012G>A	p.Gly338Ser	missense_variant	2/2		NP_001307373.1	Q8N9M5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM102	ENST00000323206.2 linkuse as main transcript	c.1012G>A	p.Gly338Ser	missense_variant	3/3	1	NM_178518.3	ENSP00000315387.1	Q8N9M5
TMEM102	ENST00000396568.1 linkuse as main transcript	c.1012G>A	p.Gly338Ser	missense_variant	2/2	2		ENSP00000379815.1	Q8N9M5
ENSG00000262624	ENST00000570444.1 linkuse as main transcript	n.249+284C>T		intron_variant		3
ENSG00000262880	ENST00000575310.1 linkuse as main transcript	n.273-4480G>A		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000917

AC:

AN:

218138

Hom.:

AF XY:

0.00000820

AC XY:

AN XY:

121942

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000206

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000691

AC:

AN:

1447184

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720258

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000849

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

The c.1012G>A (p.G338S) alteration is located in exon 3 (coding exon 2) of the TMEM102 gene. This alteration results from a G to A substitution at nucleotide position 1012, causing the glycine (G) at amino acid position 338 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.47

M_CAP

Benign

0.032

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

0.94

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.13

Sift

Benign

0.050

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.38

MutPred

0.22

Gain of glycosylation at G338 (P = 0.0161);Gain of glycosylation at G338 (P = 0.0161);

MVP

0.19

ClinPred

0.76

GERP RS

4.2

Varity_R

0.16

gMVP

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over