2-102814902-A-G

Variant summary

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

The NM_144632.5(TMEM182):ā€‹c.624A>Gā€‹(p.Ile208Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000086 ( 0 hom., cov: 32)
Exomes š‘“: 0.00016 ( 0 hom. )

Consequence

TMEM182
NM_144632.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.755
Variant links:
Genes affected
TMEM182 (HGNC:26391): (transmembrane protein 182) Predicted to be integral component of membrane. [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=0.14816535).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM182NM_144632.5 linkuse as main transcriptc.624A>G p.Ile208Met missense_variant 5/5 ENST00000412401.3 NP_653233.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM182ENST00000412401.3 linkuse as main transcriptc.624A>G p.Ile208Met missense_variant 5/51 NM_144632.5 ENSP00000394178 P1Q6ZP80-1

Frequencies

GnomAD3 genomes
AF:
0.0000856
AC:
13
AN:
151874
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000147
AC:
37
AN:
251218
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000462
Gnomad NFE exome
AF:
0.000299
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000163
AC:
238
AN:
1461698
Hom.:
0
Cov.:
30
AF XY:
0.000171
AC XY:
124
AN XY:
727144
show subpopulations
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:
0.0000562
Gnomad4 NFE exome
AF:
0.000192
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.0000856
AC:
13
AN:
151874
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000193
Hom.:
0
Bravo
AF:
0.000102
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000255
AC:
31
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2023The c.624A>G (p.I208M) alteration is located in exon 5 (coding exon 5) of the TMEM182 gene. This alteration results from a A to G substitution at nucleotide position 624, causing the isoleucine (I) at amino acid position 208 to be replaced by a methionine (M). 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
0.23
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
.;.;T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
2.0
.;.;M
MutationTaster
Benign
0.52
N;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.21
Sift
Uncertain
0.0060
D;D;D
Sift4G
Uncertain
0.022
D;D;D
Polyphen
0.40
.;B;B
Vest4
0.35
MVP
0.31
MPC
0.29
ClinPred
0.16
T
GERP RS
-2.9
Varity_R
0.24
gMVP
0.65

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: rs144729903; hg19: chr2-103431361; API