rs1046187866

Variant names:

• chr21-34669426-G-A
• rs1046187866
• NM_053277.3:c.38G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-34669426-G-A
• chr21-34669426-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053277.3(CLIC6):​c.38G>A​(p.Gly13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000243 in 1,234,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CLIC6 NM_053277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.157
• Publications: 0 publications found

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]

ACMG classification

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=0.240823).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC6	NM_053277.3	MANE Select	c.38G>A	p.Gly13Asp	missense	Exon 1 of 6	NP_444507.1	Q96NY7-2
	CLIC6	NM_001317009.2		c.38G>A	p.Gly13Asp	missense	Exon 1 of 7	NP_001303938.1	Q96NY7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC6	ENST00000349499.3	TSL:1 MANE Select	c.38G>A	p.Gly13Asp	missense	Exon 1 of 6	ENSP00000290332.4	Q96NY7-2
	CLIC6	ENST00000360731.7	TSL:1	c.38G>A	p.Gly13Asp	missense	Exon 1 of 7	ENSP00000353959.3	Q96NY7-1
	CLIC6	ENST00000954659.1		c.38G>A	p.Gly13Asp	missense	Exon 1 of 8	ENSP00000624718.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 33

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: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1082876 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 511518

African (AFR) AF: 0.00 AC: 0 AN: 22984

American (AMR) AF: 0.00 AC: 0 AN: 8462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14430

East Asian (EAS) AF: 0.00 AC: 0 AN: 26566

South Asian (SAS) AF: 0.00 AC: 0 AN: 20010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3162

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 922120

Other (OTH) AF: 0.00 AC: 0 AN: 43816

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74296

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.16
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.031
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.96	D
Vest4		0.13
MutPred		0.28		Loss of glycosylation at P18 (P = 0.2291)
MVP		0.48
MPC		1.9
ClinPred		0.39	T
GERP RS		1.4
PromoterAI		0.033	Neutral
Varity_R		0.15
gMVP		0.14
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs1046187866; hg19: chr21-36041725;