16-3501080-G-C

Position:

• chr16-3501080-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015041.3(CLUAP1):​c.13G>C​(p.Asp5His) 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. Variant has been reported in ClinVar 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: 4.85

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]

ENSG00000263212 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUAP1	NM_015041.3	c.13G>C	p.Asp5His	missense_variant	1/12	ENST00000576634.6	NP_055856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUAP1	ENST00000576634.6	c.13G>C	p.Asp5His	missense_variant	1/12	1	NM_015041.3	ENSP00000460850.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.13G>C (p.D5H) alteration is located in exon 1 (coding exon 1) of the CLUAP1 gene. This alteration results from a G to C substitution at nucleotide position 13, causing the aspartic acid (D) at amino acid position 5 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.2	M;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.7	.;.;D;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	.;.;D;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.62
MutPred		0.68		Loss of stability (P = 0.0694);Loss of stability (P = 0.0694);Loss of stability (P = 0.0694);Loss of stability (P = 0.0694);
MVP		0.69
MPC		0.31
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.87
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3551080;