GeneBe

rs1783831713

Variant names:

Variant summary

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

The NM_001366626.1(TMEM196):​c.530G>A​(p.Arg177Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TMEM196
NM_001366626.1 missense

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Publications

0 publications found
Variant links:
Genes affected
TMEM196 (HGNC:22431): (transmembrane protein 196) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.14597693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366626.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TMEM196
NM_001363562.2
MANE Select
c.*46G>A
3_prime_UTR
Exon 5 of 5NP_001350491.1B7WNR7
TMEM196
NM_001366626.1
c.530G>Ap.Arg177Lys
missense
Exon 4 of 4NP_001353555.1Q5HYL7-1
TMEM196
NM_152774.3
c.512G>Ap.Arg171Lys
missense
Exon 4 of 4NP_689987.3Q5HYL7-4

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TMEM196
ENST00000405764.7
TSL:1
c.512G>Ap.Arg171Lys
missense
Exon 4 of 4ENSP00000384234.3Q5HYL7-4
TMEM196
ENST00000405844.6
TSL:5 MANE Select
c.*46G>A
3_prime_UTR
Exon 5 of 5ENSP00000385087.2B7WNR7
TMEM196
ENST00000493519.2
TSL:5
c.308G>Ap.Arg103Lys
missense
Exon 4 of 4ENSP00000438368.1Q5HYL7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1457730
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725264
African (AFR)
AF:
0.00
AC:
0
AN:
33174
American (AMR)
AF:
0.00
AC:
0
AN:
44300
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26020
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39384
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85630
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53330
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1109910
Other (OTH)
AF:
0.00
AC:
0
AN:
60230
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
17
DANN
Uncertain
0.99
Eigen
Benign
-0.046
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.93
T
PhyloP100
2.6
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.13
Sift
Benign
0.059
T
Sift4G
Benign
0.21
T
Polyphen
0.0020
B
Vest4
0.059
MutPred
0.21
Gain of ubiquitination at R171 (P = 0.0289)
MVP
0.12
MPC
0.011
ClinPred
0.73
D
GERP RS
5.8
Mutation Taster
=82/18
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: rs1783831713; hg19: chr7-19761705; COSMIC: COSV108247197; API