rs779786023

Variant summary

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

The NM_178518.3(TMEM102):​c.235C>A​(p.Pro79Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,611,522 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P79S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM102
NM_178518.3 missense

Scores

1
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM102NM_178518.3 linkc.235C>A p.Pro79Thr missense_variant Exon 3 of 3 ENST00000323206.2 NP_848613.1 Q8N9M5
TMEM102NM_001320444.1 linkc.235C>A p.Pro79Thr 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.235C>A p.Pro79Thr missense_variant Exon 3 of 3 1 NM_178518.3 ENSP00000315387.1 Q8N9M5
ENSG00000286007ENST00000651314.1 linkn.*123C>A non_coding_transcript_exon_variant Exon 4 of 4 ENSP00000498964.1 A0A494C1D0
ENSG00000286007ENST00000651314.1 linkn.*123C>A 3_prime_UTR_variant Exon 4 of 4 ENSP00000498964.1 A0A494C1D0

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00000402
AC:
1
AN:
249032
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135046
show subpopulations
Gnomad AFR exome
AF:
0.0000625
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
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:
6.85e-7
AC:
1
AN:
1459332
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725662
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152190
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
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
Bravo
AF:
0.0000416
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.017
T;T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.82
D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.19
Sift
Uncertain
0.028
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.52
MutPred
0.54
Gain of phosphorylation at P79 (P = 0.0137);Gain of phosphorylation at P79 (P = 0.0137);
MVP
0.68
ClinPred
0.96
D
GERP RS
5.4
Varity_R
0.19
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs779786023; hg19: chr17-7339533; API