17-7436896-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178518.3(TMEM102):​c.917C>T​(p.Thr306Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 1,609,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000052 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TMEM102
NM_178518.3 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.578
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11763498).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM102NM_178518.3 linkc.917C>T p.Thr306Ile missense_variant Exon 3 of 3 ENST00000323206.2 NP_848613.1 Q8N9M5
TMEM102NM_001320444.1 linkc.917C>T p.Thr306Ile missense_variant Exon 2 of 2 NP_001307373.1 Q8N9M5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM102ENST00000323206.2 linkc.917C>T p.Thr306Ile missense_variant Exon 3 of 3 1 NM_178518.3 ENSP00000315387.1 Q8N9M5
TMEM102ENST00000396568.1 linkc.917C>T p.Thr306Ile missense_variant Exon 2 of 2 2 ENSP00000379815.1 Q8N9M5
ENSG00000262624ENST00000570444.1 linkn.250-262G>A intron_variant Intron 1 of 1 3
ENSG00000262880ENST00000575310.1 linkn.273-4575C>T intron_variant Intron 3 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.0000525
AC:
8
AN:
152266
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000136
AC:
33
AN:
242602
Hom.:
0
AF XY:
0.0000680
AC XY:
9
AN XY:
132440
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000930
Gnomad ASJ exome
AF:
0.000101
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000384
AC:
56
AN:
1457430
Hom.:
0
Cov.:
32
AF XY:
0.0000248
AC XY:
18
AN XY:
725252
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000985
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152384
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74520
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000743
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.917C>T (p.T306I) 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 917, causing the threonine (T) at amino acid position 306 to be replaced by an isoleucine (I). 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
Uncertain
0.52
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;T
Eigen
Benign
-0.046
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.25
N
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.13
Sift
Uncertain
0.028
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.44
MutPred
0.33
Loss of glycosylation at T306 (P = 0.0112);Loss of glycosylation at T306 (P = 0.0112);
MVP
0.39
ClinPred
0.18
T
GERP RS
4.2
Varity_R
0.12
gMVP
0.60

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780719919; hg19: chr17-7340215; API