17-7437258-C-T

Position:

• chr17-7437258-C-T

Variant summary

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

The NM_178518.3(TMEM102):​c.1279C>T​(p.Pro427Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,378,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 7.3e-7 (0 hom.)
• Consequence: TMEM102 NM_178518.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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]

(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=0.09505263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM102	NM_178518.3	c.1279C>T	p.Pro427Ser	missense_variant	3/3	ENST00000323206.2
TMEM102	NM_001320444.1	c.1279C>T	p.Pro427Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM102	ENST00000323206.2	c.1279C>T	p.Pro427Ser	missense_variant	3/3	1	NM_178518.3	P1
	ENST00000570444.1	n.249+17G>A		intron_variant, non_coding_transcript_variant		3
TMEM102	ENST00000396568.1	c.1279C>T	p.Pro427Ser	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1378224 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681104

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: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0074	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.25	N
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.035
Sift	Uncertain	0.024	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.058	B;B
Vest4		0.14
MutPred		0.34		Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);
MVP		0.31
ClinPred		0.38	T
GERP RS		3.0
Varity_R		0.057
gMVP		0.36

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: chr17-7340577; COSMIC: COSV53439817; COSMIC: COSV53439817;