rs201318042

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053277.3(CLIC6):​c.538G>A​(p.Val180Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CLIC6
NM_053277.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375
Variant links:
Genes affected
CLIC6 (HGNC:2065): (chloride intracellular channel 6) This gene encodes a member of the chloride intracellular channel family of proteins. The gene is part of a large triplicated region found on chromosomes 1, 6, and 21. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.047477514).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLIC6NM_053277.3 linkc.538G>A p.Val180Ile missense_variant Exon 1 of 6 ENST00000349499.3 NP_444507.1 Q96NY7-2
CLIC6NM_001317009.2 linkc.538G>A p.Val180Ile missense_variant Exon 1 of 7 NP_001303938.1 Q96NY7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLIC6ENST00000349499.3 linkc.538G>A p.Val180Ile missense_variant Exon 1 of 6 1 NM_053277.3 ENSP00000290332.4 Q96NY7-2
CLIC6ENST00000360731.7 linkc.538G>A p.Val180Ile missense_variant Exon 1 of 7 1 ENSP00000353959.3 Q96NY7-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
150468
Hom.:
0
Cov.:
30
FAILED QC
Gnomad AFR
AF:
0.0000245
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:
0.0000956
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000172
AC:
2
AN:
1163184
Hom.:
0
Cov.:
65
AF XY:
0.00
AC XY:
0
AN XY:
562138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000166
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
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000133
AC:
2
AN:
150468
Hom.:
0
Cov.:
30
AF XY:
0.0000272
AC XY:
2
AN XY:
73476
show subpopulations
Gnomad4 AFR
AF:
0.0000245
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000956
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
5.8
DANN
Uncertain
0.98
DEOGEN2
Benign
0.019
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.28
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.047
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.17
N;N
REVEL
Benign
0.0070
Sift
Benign
0.081
T;T
Sift4G
Uncertain
0.048
D;D
Polyphen
0.065
B;B
Vest4
0.084
MutPred
0.12
Gain of glycosylation at S179 (P = 0.1238);Gain of glycosylation at S179 (P = 0.1238);
MVP
0.20
MPC
1.7
ClinPred
0.056
T
GERP RS
-0.26
Varity_R
0.031
gMVP
0.023

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: rs201318042; hg19: chr21-36042225; API