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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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: 0.0 ( 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

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=0.06077695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM102	NM_178518.3 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 3 of 3	ENST00000323206.2	NP_848613.1	Q8N9M5
TMEM102	NM_001320444.1 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 2 of 2		NP_001307373.1	Q8N9M5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM102	ENST00000323206.2 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 3 of 3	1	NM_178518.3	ENSP00000315387.1	Q8N9M5
TMEM102	ENST00000396568.1 link	c.1073C>T	p.Pro358Leu	missense_variant	Exon 2 of 2	2		ENSP00000379815.1	Q8N9M5
ENSG00000262624	ENST00000570444.1 link	n.249+223G>A		intron_variant	Intron 1 of 1	3
ENSG00000262880	ENST00000575310.1 link	n.273-4419C>T		intron_variant	Intron 3 of 5	2

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

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:

0.00

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

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1073C>T (p.P358L) alteration is located in exon 3 (coding exon 2) of the TMEM102 gene. This alteration results from a C to T substitution at nucleotide position 1073, causing the proline (P) at amino acid position 358 to be replaced by a leucine (L). 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

0.083

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.8

DANN

Benign

0.88

DEOGEN2

Benign

0.031

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.015

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.012

Sift

Benign

0.12

T;T

Sift4G

Benign

0.070

T;T

Polyphen

0.044

B;B

Vest4

0.071

MutPred

0.36

Loss of glycosylation at P358 (P = 0.0479);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

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