rs1213203575

Variant names:

• chr16-3501072-C-G
• rs1213203575
• NM_015041.3:c.5C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-3501072-C-G
• chr16-3501072-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015041.3(CLUAP1):​c.5C>G​(p.Ser2Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLUAP1 NM_015041.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.5C>G	p.Ser2Cys	missense	Exon 1 of 12	NP_055856.1	Q96AJ1-1
	CLUAP1	NM_001330454.2		c.5C>G	p.Ser2Cys	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.5C>G	p.Ser2Cys	missense	Exon 1 of 12	ENSP00000460850.1	Q96AJ1-1
	CLUAP1	ENST00000341633.9	TSL:5	c.5C>G	p.Ser2Cys	missense	Exon 1 of 13	ENSP00000344392.5	J3KNW5
	CLUAP1	ENST00000969006.1		c.5C>G	p.Ser2Cys	missense	Exon 1 of 13	ENSP00000639065.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.033	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.8
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.48		Loss of disorder (P = 0.013)
MVP		0.88
MPC		0.31
ClinPred		1.0	D
GERP RS		4.9
PromoterAI		-0.057	Neutral
Varity_R		0.80
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1213203575; hg19: chr16-3551072;