rs113112766

Variant names:

• chr16-28477361-T-G
• rs113112766
• NM_001042432.2:c.*155A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-28477361-T-G
• chr16-28477361-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001042432.2(CLN3):​c.*155A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 990,702 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (23 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (11 hom.)
• Consequence: CLN3 NM_001042432.2 3_prime_UTR
• Scores: Splicing: ADA: 0.00003789
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.28
• Publications: 0 publications found

Genes affected

CLN3 (HGNC:2074): (CLN3 lysosomal/endosomal transmembrane protein, battenin) This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

CLN3 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuronal ceroid lipofuscinosis 3

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

ENSG00000261832 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-28477361-T-G is Benign according to our data. Variant chr16-28477361-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 318711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1540/152266) while in subpopulation AFR AF = 0.0356 (1479/41570). AF 95% confidence interval is 0.0341. There are 23 homozygotes in GnomAd4. There are 748 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042432.2. 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
	CLN3	NM_001042432.2	MANE Select	c.*155A>C		3_prime_UTR	Exon 16 of 16	NP_001035897.1	Q13286-1
	CLN3	NM_000086.2		c.*155A>C		3_prime_UTR	Exon 15 of 15	NP_000077.1	Q13286-1
	CLN3	NM_001286104.2		c.*155A>C		3_prime_UTR	Exon 15 of 15	NP_001273033.1	Q13286-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN3	ENST00000636147.2	TSL:1 MANE Select	c.*155A>C		3_prime_UTR	Exon 16 of 16	ENSP00000490105.1	Q13286-1
	CLN3	ENST00000359984.12	TSL:1	c.*155A>C		3_prime_UTR	Exon 15 of 15	ENSP00000353073.9	Q13286-1
	CLN3	ENST00000357806.11	TSL:1	c.*155A>C		3_prime_UTR	Exon 12 of 12	ENSP00000350457.7	Q13286-6

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1530 AN: 152148 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00117 AC: 978 AN: 838436 Hom.: 11 Cov.: 11 AF XY: 0.000930 AC XY: 400 AN XY: 430104

African (AFR) AF: 0.0353 AC: 740 AN: 20968

American (AMR) AF: 0.00181 AC: 62 AN: 34178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20876

East Asian (EAS) AF: 0.00 AC: 0 AN: 33644

South Asian (SAS) AF: 0.0000589 AC: 4 AN: 67948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35080

Middle Eastern (MID) AF: 0.00276 AC: 8 AN: 2902

European-Non Finnish (NFE) AF: 0.0000737 AC: 43 AN: 583252

Other (OTH) AF: 0.00306 AC: 121 AN: 39588

GnomAD4 genome AF: 0.0101 AC: 1540 AN: 152266 Hom.: 23 Cov.: 33 AF XY: 0.0100 AC XY: 748 AN XY: 74456

African (AFR) AF: 0.0356 AC: 1479 AN: 41570

American (AMR) AF: 0.00248 AC: 38 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67994

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.0127 Hom.: 21

Bravo AF: 0.0120

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Neuronal ceroid lipofuscinosis 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.7
DANN	Benign	0.52
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.0020
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: rs113112766; hg19: chr16-28488682;