chr13-76992289-C-T

Variant names:

• chr13-76992289-C-T
• rs112141862
• NM_006493.4:c.173+18C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006493.4(CLN5):​c.173+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,541,536 control chromosomes in the GnomAD database, including 1,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (407 hom., cov: 32)
  • Exomes 𝑓: 0.025 (777 hom.)
• Consequence: CLN5 NM_006493.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.523
• Publications: 2 publications found

Genes affected

CLN5 (HGNC:2076): (CLN5 intracellular trafficking protein) This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function.[provided by RefSeq, Oct 2008]

CLN5 Gene-Disease associations (from GenCC):

• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuronal ceroid lipofuscinosis 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health

ENSG00000283208 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 13-76992289-C-T is Benign according to our data. Variant chr13-76992289-C-T is described in ClinVar as Benign. ClinVar VariationId is 95397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLN5	NM_006493.4	c.173+18C>T		intron_variant	Intron 1 of 3	ENST00000377453.9	NP_006484.2
CLN5	NM_001366624.2	c.173+18C>T		intron_variant	Intron 1 of 4		NP_001353553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLN5	ENST00000377453.9	c.173+18C>T		intron_variant	Intron 1 of 3	1	NM_006493.4	ENSP00000366673.5
ENSG00000283208	ENST00000638147.2	c.173+18C>T		intron_variant	Intron 1 of 4	5		ENSP00000490953.2

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8461 AN: 151502 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0407

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0509

GnomAD2 exomes AF: 0.0379 AC: 5243 AN: 138422 AF XY: 0.0349

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0393

Gnomad ASJ exome AF: 0.0408

Gnomad EAS exome AF: 0.0702

Gnomad FIN exome AF: 0.0577

Gnomad NFE exome AF: 0.0274

Gnomad OTH exome AF: 0.0348

GnomAD4 exome AF: 0.0252 AC: 35051 AN: 1389920 Hom.: 777 Cov.: 34 AF XY: 0.0248 AC XY: 17064 AN XY: 687406

African (AFR) AF: 0.127 AC: 3999 AN: 31398

American (AMR) AF: 0.0364 AC: 1293 AN: 35476

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 926 AN: 24586

East Asian (EAS) AF: 0.0565 AC: 2079 AN: 36810

South Asian (SAS) AF: 0.0131 AC: 1045 AN: 79988

European-Finnish (FIN) AF: 0.0548 AC: 1968 AN: 35922

Middle Eastern (MID) AF: 0.0562 AC: 227 AN: 4040

European-Non Finnish (NFE) AF: 0.0199 AC: 21528 AN: 1083758

Other (OTH) AF: 0.0343 AC: 1986 AN: 57942

GnomAD4 genome AF: 0.0560 AC: 8484 AN: 151616 Hom.: 407 Cov.: 32 AF XY: 0.0566 AC XY: 4191 AN XY: 74070

African (AFR) AF: 0.128 AC: 5279 AN: 41296

American (AMR) AF: 0.0314 AC: 479 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0407 AC: 141 AN: 3466

East Asian (EAS) AF: 0.0579 AC: 294 AN: 5074

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4806

European-Finnish (FIN) AF: 0.0481 AC: 505 AN: 10494

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0234 AC: 1587 AN: 67908

Other (OTH) AF: 0.0504 AC: 106 AN: 2104

Alfa AF: 0.0441 Hom.: 59

Bravo AF: 0.0580

Asia WGS AF: 0.0430 AC: 153 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:8

Jul 12, 2022

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 03, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 19, 2012

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Neuronal ceroid lipofuscinosis Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.91
PhyloP100		-0.52
PromoterAI		0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs112141862; hg19: chr13-77566424;