Variant chr17-7436615-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178518.3(TMEM102):c.636C>G(p.Asp212Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 6.8e-7 ( 0 hom. )

Consequence

TMEM102
NM_178518.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.602

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04578033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM102	NM_178518.3 linkuse as main transcript	c.636C>G	p.Asp212Glu	missense_variant	3/3	ENST00000323206.2	NP_848613.1	Q8N9M5
TMEM102	NM_001320444.1 linkuse as main transcript	c.636C>G	p.Asp212Glu	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.636C>G	p.Asp212Glu	missense_variant	3/3	1	NM_178518.3	ENSP00000315387.1	Q8N9M5
TMEM102	ENST00000396568.1 linkuse as main transcript	c.636C>G	p.Asp212Glu	missense_variant	2/2	2		ENSP00000379815.1	Q8N9M5
ENSG00000262624	ENST00000570444.1 linkuse as main transcript	n.269G>C		non_coding_transcript_exon_variant	2/2	3
ENSG00000262880	ENST00000575310.1 linkuse as main transcript	n.273-4856C>G		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727130

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 14, 2023

The c.636C>G (p.D212E) alteration is located in exon 3 (coding exon 2) of the TMEM102 gene. This alteration results from a C to G substitution at nucleotide position 636, causing the aspartic acid (D) at amino acid position 212 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.8

DANN

Benign

0.84

DEOGEN2

Benign

0.0064

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.19

M_CAP

Benign

0.0093

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.064

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.049

D;D

Polyphen

0.0020

B;B

Vest4

0.014

MutPred

0.077

Gain of glycosylation at P210 (P = 0.1309);Gain of glycosylation at P210 (P = 0.1309);

MVP

0.22

ClinPred

0.058

GERP RS

-1.2

Varity_R

0.13

gMVP

0.044

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over