Variant chr16-3501075-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015041.3(CLUAP1):c.8T>C(p.Phe3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,446,268 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CLUAP1
NM_015041.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Variant links:

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 links:

ENSG00000263212 (HGNC:):

ENSG00000263212 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUAP1	NM_015041.3 linkuse as main transcript	c.8T>C	p.Phe3Ser	missense_variant	1/12	ENST00000576634.6	NP_055856.1	Q96AJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUAP1	ENST00000576634.6 linkuse as main transcript	c.8T>C	p.Phe3Ser	missense_variant	1/12	1	NM_015041.3	ENSP00000460850.1		Q96AJ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

228616

Hom.:

AF XY:

0.00

AC XY:

AN XY:

124928

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000951

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719270

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2021

This variant has not been reported in the literature in individuals with CLUAP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 3 of the CLUAP1 protein (p.Phe3Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

M;.;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.0

.;.;D;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

.;.;D;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.99

D;.;.;.

Vest4

0.77

MutPred

0.65

Gain of disorder (P = 0.0096);Gain of disorder (P = 0.0096);Gain of disorder (P = 0.0096);Gain of disorder (P = 0.0096);

MVP

0.77

MPC

0.33

ClinPred

1.0

GERP RS

4.9

Varity_R

0.90

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over