rs150143344

Variant names:

• chr6-45903121-G-A
• rs150143344
• NM_016929.5:c.723C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-45903121-G-A
• chr6-45903121-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_016929.5(CLIC5):​c.723C>T​(p.Tyr241Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,614,048 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (3 hom.)
• Consequence: CLIC5 NM_016929.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.593
• Publications: 1 publications found

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]

CLIC5 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 103

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 6-45903121-G-A is Benign according to our data. Variant chr6-45903121-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2152715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.593 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016929.5. 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
	CLIC5	NM_016929.5	MANE Select	c.723C>T	p.Tyr241Tyr	synonymous	Exon 6 of 6	NP_058625.2	Q53G01
	CLIC5	NM_001114086.2		c.1200C>T	p.Tyr400Tyr	synonymous	Exon 6 of 6	NP_001107558.1	Q9NZA1-1
	CLIC5	NM_001370650.1		c.1200C>T	p.Tyr400Tyr	synonymous	Exon 7 of 7	NP_001357579.1	Q9NZA1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	ENST00000339561.12	TSL:1 MANE Select	c.723C>T	p.Tyr241Tyr	synonymous	Exon 6 of 6	ENSP00000344165.6	Q9NZA1-2
	CLIC5	ENST00000185206.12	TSL:1	c.1200C>T	p.Tyr400Tyr	synonymous	Exon 6 of 6	ENSP00000185206.6	Q9NZA1-1
	CLIC5	ENST00000644324.1		c.623+10657C>T		intron	N/A	ENSP00000495186.1	A0A2R8Y615

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 251346 AF XY: 0.000125

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000163 AC: 239 AN: 1461848 Hom.: 3 Cov.: 30 AF XY: 0.000194 AC XY: 141 AN XY: 727222

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86256

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000172 AC: 191 AN: 1111986

Other (OTH) AF: 0.000315 AC: 19 AN: 60394

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.0000491

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.59
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: rs150143344; hg19: chr6-45870858; COSMIC: COSV51762782;