6-31736267-C-G

Variant names:

• chr6-31736267-C-G
• NM_001288.6:c.34G>C
• CLIC1 p.Val12Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288.6(CLIC1):​c.34G>C​(p.Val12Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V12M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLIC1 NM_001288.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• Publications: 0 publications found

Genes affected

CLIC1 (HGNC:2062): (chloride intracellular channel 1) Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2049838).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288.6. 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
	CLIC1	NM_001288.6	MANE Select	c.34G>C	p.Val12Leu	missense	Exon 1 of 6	NP_001279.2
	CLIC1	NM_001287593.1		c.34G>C	p.Val12Leu	missense	Exon 2 of 7	NP_001274522.1	O00299
	CLIC1	NM_001287594.3		c.34G>C	p.Val12Leu	missense	Exon 2 of 7	NP_001274523.1	O00299

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC1	ENST00000375784.8	TSL:1 MANE Select	c.34G>C	p.Val12Leu	missense	Exon 1 of 6	ENSP00000364940.3	O00299
	CLIC1	ENST00000375780.6	TSL:1	c.34G>C	p.Val12Leu	missense	Exon 2 of 7	ENSP00000364935.2	O00299
	CLIC1	ENST00000864998.1		c.34G>C	p.Val12Leu	missense	Exon 1 of 6	ENSP00000535057.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Benign	0.030	D
Sift4G	Benign	0.083	T
PromoterAI		-0.11	Neutral
Varity_R		0.47
gMVP		0.60
Mutation Taster		=41/59	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-31704044;