17-7436580-G-A

Variant names:

• chr17-7436580-G-A
• rs892855307
• NM_178518.3:c.601G>A

Variant summary

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

The NM_178518.3(TMEM102):​c.601G>A​(p.Glu201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM102 NM_178518.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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=0.08064729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM102	NM_178518.3	c.601G>A	p.Glu201Lys	missense_variant	Exon 3 of 3	ENST00000323206.2	NP_848613.1
TMEM102	NM_001320444.1	c.601G>A	p.Glu201Lys	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.601G>A	p.Glu201Lys	missense_variant	Exon 3 of 3	1	NM_178518.3	ENSP00000315387.1
TMEM102	ENST00000396568.1	c.601G>A	p.Glu201Lys	missense_variant	Exon 2 of 2	2		ENSP00000379815.1
ENSG00000262624	ENST00000570444.1	n.304C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
ENSG00000262880	ENST00000575310.1	n.273-4891G>A		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461650 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727130

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601G>A (p.E201K) alteration is located in exon 3 (coding exon 2) of the TMEM102 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the glutamic acid (E) at amino acid position 201 to be replaced by a lysine (K). 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	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0066	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.62	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.93	N;N
REVEL	Benign	0.032
Sift	Benign	0.19	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.15	B;B
Vest4		0.13
MutPred		0.20		Gain of ubiquitination at E201 (P = 0.001);Gain of ubiquitination at E201 (P = 0.001);
MVP		0.28
ClinPred		0.10	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.28

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: rs892855307; hg19: chr17-7339899;