7-150793995-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001101312.2(TMEM176B):​c.281G>T​(p.Ser94Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. S94N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM176B
NM_001101312.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

2 publications found
Variant links:
Genes affected
TMEM176B (HGNC:29596): (transmembrane protein 176B) Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be located in nuclear membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11708316).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM176BNM_001101312.2 linkc.281G>T p.Ser94Ile missense_variant Exon 3 of 7 ENST00000326442.10 NP_001094782.1 Q3YBM2-1A0A090N7V7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM176BENST00000326442.10 linkc.281G>T p.Ser94Ile missense_variant Exon 3 of 7 1 NM_001101312.2 ENSP00000318409.5 Q3YBM2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250550
AF XY:
0.00000739
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461384
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727016
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33464
American (AMR)
AF:
0.00
AC:
0
AN:
44634
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26088
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86206
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111766
Other (OTH)
AF:
0.00
AC:
0
AN:
60360
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
6.7
DANN
Benign
0.56
DEOGEN2
Benign
0.031
T;T;T;T;T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.28
.;.;.;T;.
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.12
T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.34
N;N;N;N;N
PhyloP100
0.21
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.75
N;N;N;N;N
REVEL
Benign
0.043
Sift
Benign
0.43
T;T;T;T;T
Sift4G
Benign
0.40
T;T;T;T;T
Polyphen
0.14
B;B;B;B;B
Vest4
0.19
MutPred
0.43
Loss of glycosylation at S94 (P = 0.08);Loss of glycosylation at S94 (P = 0.08);Loss of glycosylation at S94 (P = 0.08);Loss of glycosylation at S94 (P = 0.08);Loss of glycosylation at S94 (P = 0.08);
MVP
0.34
MPC
0.050
ClinPred
0.14
T
GERP RS
3.0
Varity_R
0.049
gMVP
0.23
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs770220387; hg19: chr7-150491083; API