chr17-7436842-C-T

Variant names:

• chr17-7436842-C-T
• rs1370573011
• NM_178518.3:c.863C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178518.3(TMEM102):​c.863C>T​(p.Pro288Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000034 (0 hom.)
• Consequence: TMEM102 NM_178518.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40155208).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178518.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM102	NM_178518.3	MANE Select	c.863C>T	p.Pro288Leu	missense	Exon 3 of 3	NP_848613.1	Q8N9M5
	TMEM102	NM_001320444.1		c.863C>T	p.Pro288Leu	missense	Exon 2 of 2	NP_001307373.1	Q8N9M5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM102	ENST00000323206.2	TSL:1 MANE Select	c.863C>T	p.Pro288Leu	missense	Exon 3 of 3	ENSP00000315387.1	Q8N9M5
	TMEM102	ENST00000396568.1	TSL:2	c.863C>T	p.Pro288Leu	missense	Exon 2 of 2	ENSP00000379815.1	Q8N9M5
	TMEM102	ENST00000860243.1		c.710C>T	p.Pro237Leu	missense	Exon 3 of 3	ENSP00000530302.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460604 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726628

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111984

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.27	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.57		Gain of helix (P = 0.0854)
MVP		0.67
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.22
gMVP		0.62
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs1370573011; hg19: chr17-7340161;