17-7436734-C-T

Variant names:

• chr17-7436734-C-T
• rs1908039122
• NM_178518.3:c.755C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178518.3(TMEM102):​c.755C>T​(p.Ser252Leu) 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. 15/20 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)
• Consequence: TMEM102 NM_178518.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0840

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]

ENSG00000262624 (HGNC:):

ACMG classification

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=0.06042528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM102	NM_178518.3	c.755C>T	p.Ser252Leu	missense_variant	Exon 3 of 3	ENST00000323206.2	NP_848613.1
TMEM102	NM_001320444.1	c.755C>T	p.Ser252Leu	missense_variant	Exon 2 of 2		NP_001307373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM102	ENST00000323206.2	c.755C>T	p.Ser252Leu	missense_variant	Exon 3 of 3	1	NM_178518.3	ENSP00000315387.1
TMEM102	ENST00000396568.1	c.755C>T	p.Ser252Leu	missense_variant	Exon 2 of 2	2		ENSP00000379815.1
ENSG00000262624	ENST00000570444.1	n.250-100G>A		intron_variant	Intron 1 of 1	3
ENSG00000262880	ENST00000575310.1	n.273-4737C>T		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.755C>T (p.S252L) 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 755, causing the serine (S) at amino acid position 252 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	0.077
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.0020	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.091	N
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.015
Sift	Benign	0.13	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0040	B;B
Vest4		0.089
MutPred		0.33		Gain of stability (P = 0.0121);Gain of stability (P = 0.0121);
MVP		0.21
ClinPred		0.037	T
GERP RS		-0.039
Varity_R		0.14
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

LitVar

Other links and lift over

dbSNP: rs1908039122; hg19: chr17-7340053;