17-7437139-C-G

Position:

• chr17-7437139-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000323206.2(TMEM102):​c.1160C>G​(p.Ala387Gly) 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. 12/20 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 ENST00000323206.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13856673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM102	NM_178518.3	c.1160C>G	p.Ala387Gly	missense_variant	3/3	ENST00000323206.2	NP_848613.1
TMEM102	NM_001320444.1	c.1160C>G	p.Ala387Gly	missense_variant	2/2		NP_001307373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM102	ENST00000323206.2	c.1160C>G	p.Ala387Gly	missense_variant	3/3	1	NM_178518.3	ENSP00000315387.1
TMEM102	ENST00000396568.1	c.1160C>G	p.Ala387Gly	missense_variant	2/2	2		ENSP00000379815.1
ENSG00000262624	ENST00000570444.1	n.249+136G>C		intron_variant		3
ENSG00000262880	ENST00000575310.1	n.273-4332C>G		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.1160C>G (p.A387G) 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 1160, causing the alanine (A) at amino acid position 387 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	0.037
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.30	N
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	0.81	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.049
Sift	Benign	0.45	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.61	P;P
Vest4		0.18
MutPred		0.28		Gain of catalytic residue at A387 (P = 0.0696);Gain of catalytic residue at A387 (P = 0.0696);
MVP		0.35
ClinPred		0.68	D
GERP RS		4.1
Varity_R		0.14
gMVP		0.29

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.

Other links and lift over

hg19: chr17-7340458;