Variant 17-7436034-A-C 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.163A>C(p.Lys55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,326 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000027 ( 1 hom. )

Consequence

TMEM102
NM_178518.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.658

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:

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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=0.05596754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM102	NM_178518.3 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	2/3	ENST00000323206.2	NP_848613.1
TMEM102	NM_001320444.1 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	1/2		NP_001307373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM102	ENST00000323206.2 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	2/3	1	NM_178518.3	ENSP00000315387	P1
TMEM102	ENST00000396568.1 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	1/2	2		ENSP00000379815	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249634

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461326

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

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

May 30, 2024

The c.163A>C (p.K55Q) alteration is located in exon 2 (coding exon 1) of the TMEM102 gene. This alteration results from a A to C substitution at nucleotide position 163, causing the lysine (K) at amino acid position 55 to be replaced by a glutamine (Q). 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

0.093

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.0038

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.53

M_CAP

Benign

0.0022

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.94

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.031

Sift

Benign

0.72

T;T

Sift4G

Uncertain

0.026

D;D

Polyphen

0.0030

B;B

Vest4

0.17

MutPred

0.29

Loss of ubiquitination at K55 (P = 0.0081);Loss of ubiquitination at K55 (P = 0.0081);

MVP

0.28

ClinPred

0.051

GERP RS

-1.3

Varity_R

0.081

gMVP

0.25

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