rs752208168

Variant names:

• chr21-34669919-C-A
• rs752208168
• NM_053277.3:c.531C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-34669919-C-A
• chr21-34669919-C-G
• chr21-34669919-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_053277.3(CLIC6):​c.531C>A​(p.Gly177Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 26)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: CLIC6 NM_053277.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-2.96 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC6	NM_053277.3	c.531C>A	p.Gly177Gly	synonymous_variant	Exon 1 of 6	ENST00000349499.3	NP_444507.1
CLIC6	NM_001317009.2	c.531C>A	p.Gly177Gly	synonymous_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.531C>A	p.Gly177Gly	synonymous_variant	Exon 1 of 6	1	NM_053277.3	ENSP00000290332.4
CLIC6	ENST00000360731.7	c.531C>A	p.Gly177Gly	synonymous_variant	Exon 1 of 7	1		ENSP00000353959.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 9.18e-7 AC: 1 AN: 1089032 Hom.: 0 Cov.: 65 AF XY: 0.00000192 AC XY: 1 AN XY: 520990

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: 0.0000260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.2
DANN	Benign	0.69

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: rs752208168; hg19: chr21-36042218;