Variant rs1004284755 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_053277.3(CLIC6):c.178G>A(p.Ala60Thr) 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. 13/21 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLIC6
NM_053277.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.984

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:

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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=0.059836745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC6	NM_053277.3 link	c.178G>A	p.Ala60Thr	missense_variant	Exon 1 of 6	ENST00000349499.3	NP_444507.1	Q96NY7-2
CLIC6	NM_001317009.2 link	c.178G>A	p.Ala60Thr	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.178G>A	p.Ala60Thr	missense_variant	Exon 1 of 6	1	NM_053277.3	ENSP00000290332.4		Q96NY7-2
CLIC6	ENST00000360731.7 link	c.178G>A	p.Ala60Thr	missense_variant	Exon 1 of 7	1		ENSP00000353959.3		Q96NY7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1105828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

525142

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.:

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.51

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.048

D;D

Polyphen

0.021

B;B

Vest4

0.065

MutPred

0.15

Gain of phosphorylation at A60 (P = 0.0106);Gain of phosphorylation at A60 (P = 0.0106);

MVP

0.32

MPC

1.5

ClinPred

0.13

GERP RS

0.14

Varity_R

0.097

gMVP

0.054

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