NM_001288.6:c.276G>C

Variant names:

• chr6-31733672-C-G
• NM_001288.6:c.276G>C
• CLIC1 p.Arg92Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001288.6(CLIC1):​c.276G>C​(p.Arg92Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R92G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLIC1 NM_001288.6 missense, splice_region
• Scores: Splicing: ADA: 0.9540
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3615836).

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.276G>C	p.Arg92Ser	missense splice_region	Exon 4 of 6	NP_001279.2
	CLIC1	NM_001287593.1		c.276G>C	p.Arg92Ser	missense splice_region	Exon 5 of 7	NP_001274522.1	O00299
	CLIC1	NM_001287594.3		c.276G>C	p.Arg92Ser	missense splice_region	Exon 5 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.276G>C	p.Arg92Ser	missense splice_region	Exon 4 of 6	ENSP00000364940.3	O00299
	CLIC1	ENST00000375780.6	TSL:1	c.276G>C	p.Arg92Ser	missense splice_region	Exon 5 of 7	ENSP00000364935.2	O00299
	CLIC1	ENST00000864998.1		c.276G>C	p.Arg92Ser	missense splice_region	Exon 4 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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.88	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.0
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.30
Sift	Benign	0.091	T
Sift4G	Benign	0.26	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.81
gMVP		0.68
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Pathogenic	0.78
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: chr6-31701449;