rs186952765

Variant names:

• chr21-34669521-G-A
• rs186952765
• NM_053277.3:c.133G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-34669521-G-A
• chr21-34669521-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053277.3(CLIC6):​c.133G>A​(p.Glu45Lys) 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. 12/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLIC6 NM_053277.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.146005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC6	NM_053277.3	c.133G>A	p.Glu45Lys	missense_variant	Exon 1 of 6	ENST00000349499.3	NP_444507.1
CLIC6	NM_001317009.2	c.133G>A	p.Glu45Lys	missense_variant	Exon 1 of 7		NP_001303938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC6	ENST00000349499.3	c.133G>A	p.Glu45Lys	missense_variant	Exon 1 of 6	1	NM_053277.3	ENSP00000290332.4
CLIC6	ENST00000360731.7	c.133G>A	p.Glu45Lys	missense_variant	Exon 1 of 7	1		ENSP00000353959.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1088772 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 515008

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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.53	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.93	N;N
REVEL	Benign	0.032
Sift	Benign	0.094	T;T
Sift4G	Uncertain	0.024	D;D
Polyphen		0.76	P;P
Vest4		0.077
MutPred		0.25		Gain of glycosylation at E45 (P = 0.0046);Gain of glycosylation at E45 (P = 0.0046);
MVP		0.40
MPC		1.7
ClinPred		0.29	T
GERP RS		2.3
Varity_R		0.059
gMVP		0.18

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

Other links and lift over

dbSNP: rs186952765; hg19: chr21-36041820;