chr21-34669629-G-C

Variant names:

• chr21-34669629-G-C
• NM_053277.3:c.241G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053277.3(CLIC6):​c.241G>C​(p.Gly81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 1,136,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000018 (0 hom.)
• Consequence: CLIC6 NM_053277.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06481141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC6	NM_053277.3	c.241G>C	p.Gly81Arg	missense_variant	Exon 1 of 6	ENST00000349499.3	NP_444507.1
CLIC6	NM_001317009.2	c.241G>C	p.Gly81Arg	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.241G>C	p.Gly81Arg	missense_variant	Exon 1 of 6	1	NM_053277.3	ENSP00000290332.4
CLIC6	ENST00000360731.7	c.241G>C	p.Gly81Arg	missense_variant	Exon 1 of 7	1		ENSP00000353959.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1136230 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 542816

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: 0.00000210

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.5
DANN	Benign	0.58
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.099
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.0030	B;B
Vest4		0.063
MutPred		0.34		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);
MVP		0.16
MPC		1.8
ClinPred		0.053	T
GERP RS		-2.7
Varity_R		0.047
gMVP		0.049

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-36041928;