rs35822882

Variant names:

• chr6-45949262-G-C
• rs35822882
• NM_016929.5:c.293C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-45949262-G-C
• chr6-45949262-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016929.5(CLIC5):​c.293C>G​(p.Pro98Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P98H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLIC5 NM_016929.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.97

Genes affected

CLIC5 (HGNC:13517): (chloride intracellular channel 5) This gene encodes a member of the chloride intracellular channel (CLIC) family of chloride ion channels. The encoded protein associates with actin-based cytoskeletal structures and may play a role in multiple processes including hair cell stereocilia formation, myoblast proliferation and glomerular podocyte and endothelial cell maintenance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.293C>G	p.Pro98Arg	missense_variant	Exon 3 of 6	ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.293C>G	p.Pro98Arg	missense_variant	Exon 3 of 6	1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460908 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726714

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33462

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44674

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26112

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39666

Gnomad4 SAS exome AF: 0.0000116 AC: 1 AN: 86154

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53304

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 1111452

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;.;T;.;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.75	D;D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.7	.;.;M;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-8.2	.;.;D;D;D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	.;.;D;D;D
Sift4G	Pathogenic	0.0010	.;.;D;D;D
Polyphen		1.0	.;.;D;.;.
Vest4		0.77, 0.80, 0.71
MutPred		0.39		.;.;Gain of solvent accessibility (P = 0.0411);.;.;
MVP		0.72
MPC		0.57
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.91
gMVP		0.87
Mutation Taster		=50/50

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

LitVar

Other links and lift over

dbSNP: rs35822882; hg19: chr6-45916999;