NM_015041.3:c.23-17T>C

Variant names:

• chr16-3504703-T-C
• rs769096900
• NM_015041.3:c.23-17T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015041.3(CLUAP1):​c.23-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000049 in 1,225,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: CLUAP1 NM_015041.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

CLUAP1 (HGNC:19009): (clusterin associated protein 1) The protein encoded by this gene contains a single coiled-coil region. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

CLUAP1 Gene-Disease associations (from GenCC):

• Leber congenital amaurosis

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ENSG00000263212 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-3504703-T-C is Benign according to our data. Variant chr16-3504703-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1567212.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015041.3. 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
	CLUAP1	NM_015041.3	MANE Select	c.23-17T>C		intron	N/A	NP_055856.1	Q96AJ1-1
	CLUAP1	NM_001330454.2		c.23-17T>C		intron	N/A	NP_001317383.1	J3KNW5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUAP1	ENST00000576634.6	TSL:1 MANE Select	c.23-17T>C		intron	N/A	ENSP00000460850.1	Q96AJ1-1
	CLUAP1	ENST00000341633.9	TSL:5	c.23-17T>C		intron	N/A	ENSP00000344392.5	J3KNW5
	CLUAP1	ENST00000969006.1		c.23-17T>C		intron	N/A	ENSP00000639065.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251254 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000490 AC: 6 AN: 1225028 Hom.: 0 Cov.: 18 AF XY: 0.00000482 AC XY: 3 AN XY: 622108

African (AFR) AF: 0.00 AC: 0 AN: 28740

American (AMR) AF: 0.00 AC: 0 AN: 44410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24776

East Asian (EAS) AF: 0.00 AC: 0 AN: 38636

South Asian (SAS) AF: 0.00 AC: 0 AN: 81486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5382

European-Non Finnish (NFE) AF: 0.00000670 AC: 6 AN: 895848

Other (OTH) AF: 0.00 AC: 0 AN: 52438

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.47
PhyloP100		3.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs769096900; hg19: chr16-3554703;