16-3501081-A-C

Variant names:

• chr16-3501081-A-C
• rs772659372
• NM_015041.3:c.14A>C

Variant summary

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

The NM_015041.3(CLUAP1):​c.14A>C​(p.Asp5Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D5H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLUAP1 NM_015041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• 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: 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, 0.759

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.14A>C	p.Asp5Ala	missense	Exon 1 of 12	NP_055856.1	Q96AJ1-1
	CLUAP1	NM_001330454.2		c.14A>C	p.Asp5Ala	missense	Exon 1 of 13	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.14A>C	p.Asp5Ala	missense	Exon 1 of 12	ENSP00000460850.1	Q96AJ1-1
	CLUAP1	ENST00000341633.9	TSL:5	c.14A>C	p.Asp5Ala	missense	Exon 1 of 13	ENSP00000344392.5	J3KNW5
	CLUAP1	ENST00000969006.1		c.14A>C	p.Asp5Ala	missense	Exon 1 of 13	ENSP00000639065.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.68		Gain of helix (P = 0.0425)
MVP		0.68
MPC		0.13
ClinPred		1.0	D
GERP RS		4.9
PromoterAI		-0.16	Neutral
Varity_R		0.72
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs772659372; hg19: chr16-3551081; COSMIC: COSV108874018; COSMIC: COSV108874018;