NM_001289.6:c.478C>T

Variant names:

• chrX-155279253-G-A
• NM_001289.6:c.478C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001289.6(CLIC2):​c.478C>T​(p.Pro160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,008 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: CLIC2 NM_001289.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

Genes affected

CLIC2 (HGNC:2063): (chloride intracellular channel 2) This gene encodes a chloride intracellular channel protein. 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. This protein plays a role in inhibiting the function of ryanodine receptor 2. A mutation in this gene is the cause of an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07618192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC2	NM_001289.6	c.478C>T	p.Pro160Ser	missense_variant	Exon 5 of 6	ENST00000369449.7	NP_001280.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC2	ENST00000369449.7	c.478C>T	p.Pro160Ser	missense_variant	Exon 5 of 6	1	NM_001289.6	ENSP00000358460.2
CLIC2	ENST00000321926.4	c.352C>T	p.Pro118Ser	missense_variant	Exon 4 of 4	3		ENSP00000318558.4
CLIC2	ENST00000465553.5	n.593C>T		non_coding_transcript_exon_variant	Exon 5 of 7	3
CLIC2	ENST00000491205.1	n.*16C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095008 Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 1 AN XY: 360482

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: 0.0000247

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.15	T;T
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	-0.34	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.096
Sift	Benign	0.24	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.067	B;.
Vest4		0.080
MutPred		0.35		Gain of phosphorylation at P160 (P = 0.0262);.;
MVP		1.0
MPC		0.59
ClinPred		0.15	T
GERP RS		0.56
Varity_R		0.15
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chrX-154508542;