rs1301743676

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_053277.3(CLIC6):​c.128G>A​(p.Gly43Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 33)
Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

CLIC6
NM_053277.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.993
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050752044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLIC6NM_053277.3 linkc.128G>A p.Gly43Glu missense_variant Exon 1 of 6 ENST00000349499.3 NP_444507.1 Q96NY7-2
CLIC6NM_001317009.2 linkc.128G>A p.Gly43Glu 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.128G>A p.Gly43Glu missense_variant Exon 1 of 6 1 NM_053277.3 ENSP00000290332.4 Q96NY7-2
CLIC6ENST00000360731.7 linkc.128G>A p.Gly43Glu missense_variant Exon 1 of 7 1 ENSP00000353959.3 Q96NY7-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151974
Hom.:
0
Cov.:
33
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:
0.00318
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
9.18e-7
AC:
1
AN:
1089038
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
515158
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
12
DANN
Benign
0.95
DEOGEN2
Benign
0.0042
T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.33
T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.051
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.25
N;N
REVEL
Benign
0.0020
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.0
B;B
Vest4
0.12
MutPred
0.26
Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);
MVP
0.12
MPC
1.9
ClinPred
0.043
T
GERP RS
-1.4
Varity_R
0.10
gMVP
0.094

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-36041815; API