rs927788428

Variant names:

• chr21-34669629-G-A
• rs927788428
• NM_053277.3:c.241G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-34669629-G-A
• chr21-34669629-G-C
• chr21-34669629-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053277.3(CLIC6):​c.241G>A​(p.Gly81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,288,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: CLIC6 NM_053277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.01
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057021707).

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.241G>A	p.Gly81Ser	missense	Exon 1 of 6	NP_444507.1	Q96NY7-2
	CLIC6	NM_001317009.2		c.241G>A	p.Gly81Ser	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.241G>A	p.Gly81Ser	missense	Exon 1 of 6	ENSP00000290332.4	Q96NY7-2
	CLIC6	ENST00000360731.7	TSL:1	c.241G>A	p.Gly81Ser	missense	Exon 1 of 7	ENSP00000353959.3	Q96NY7-1
	CLIC6	ENST00000954659.1		c.241G>A	p.Gly81Ser	missense	Exon 1 of 8	ENSP00000624718.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152018 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.0000736

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000264 AC: 30 AN: 1136230 Hom.: 0 Cov.: 30 AF XY: 0.0000295 AC XY: 16 AN XY: 542816

African (AFR) AF: 0.00 AC: 0 AN: 23202

American (AMR) AF: 0.000230 AC: 2 AN: 8710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15476

East Asian (EAS) AF: 0.000112 AC: 3 AN: 26670

South Asian (SAS) AF: 0.00 AC: 0 AN: 34874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25178

Middle Eastern (MID) AF: 0.000325 AC: 1 AN: 3078

European-Non Finnish (NFE) AF: 0.0000241 AC: 23 AN: 952902

Other (OTH) AF: 0.0000217 AC: 1 AN: 46140

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41528

American (AMR) AF: 0.000392 AC: 6 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000756

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	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.9
DANN	Benign	0.82
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.15
Sift	Benign	0.14	T
Sift4G	Uncertain	0.027	D
Polyphen		0.085	B
Vest4		0.089
MutPred		0.21		Gain of phosphorylation at G81 (P = 0.0115)
MVP		0.15
MPC		1.6
ClinPred		0.057	T
GERP RS		-2.7
PromoterAI		-0.0085	Neutral
Varity_R		0.045
gMVP		0.074
Mutation Taster		=100/0	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: rs927788428; hg19: chr21-36041928;