dbSNP rs201318042: CLIC6:p.Val180Ile (chr21-34669926-G-A) – ACMG Classification: Likely_benign (-4 pts)

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

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]

CLIC6 links:

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
CLIC6	NM_053277.3 link	c.538G>A	p.Val180Ile	missense_variant	Exon 1 of 6	ENST00000349499.3	NP_444507.1	Q96NY7-2
CLIC6	NM_001317009.2 link	c.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
CLIC6	ENST00000349499.3 link	c.538G>A	p.Val180Ile	missense_variant	Exon 1 of 6	1	NM_053277.3	ENSP00000290332.4		Q96NY7-2
CLIC6	ENST00000360731.7 link	c.538G>A	p.Val180Ile	missense_variant	Exon 1 of 7	1		ENSP00000353959.3		Q96NY7-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150468

Hom.:

Cov.:

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:

AN:

1163184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

AN:

150468

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

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

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

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N

PrimateAI

Uncertain

0.56

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over