chr21-34669919-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. Synonymous variant affecting the same amino acid position (i.e. G177G) has been classified as Likely benign.

• 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
• 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: Likely_benign. The variant received -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.

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.531C>A	p.Gly177Gly	synonymous	Exon 1 of 6	NP_444507.1	Q96NY7-2
	CLIC6	NM_001317009.2		c.531C>A	p.Gly177Gly	synonymous	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.531C>A	p.Gly177Gly	synonymous	Exon 1 of 6	ENSP00000290332.4	Q96NY7-2
	CLIC6	ENST00000360731.7	TSL:1	c.531C>A	p.Gly177Gly	synonymous	Exon 1 of 7	ENSP00000353959.3	Q96NY7-1
	CLIC6	ENST00000954659.1		c.531C>A	p.Gly177Gly	synonymous	Exon 1 of 8	ENSP00000624718.1

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

African (AFR) AF: 0.00 AC: 0 AN: 21420

American (AMR) AF: 0.00 AC: 0 AN: 8510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12910

East Asian (EAS) AF: 0.00 AC: 0 AN: 20550

South Asian (SAS) AF: 0.0000260 AC: 1 AN: 38490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2806

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920252

Other (OTH) AF: 0.00 AC: 0 AN: 42540

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		-3.0

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: rs752208168; hg19: chr21-36042218;