Genetic Variant NM_015041.3:c.5C>T (chr16-3501072-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_015041.3(CLUAP1):c.5C>T(p.Ser2Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,447,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S2C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CLUAP1
NM_015041.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Leber congenital amaurosis
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

CLUAP1 links:

ENSG00000263212 (HGNC:):

ENSG00000263212 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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>T	p.Ser2Phe	missense	Exon 1 of 12	NP_055856.1	Q96AJ1-1
	CLUAP1	NM_001330454.2		c.5C>T	p.Ser2Phe	missense	Exon 1 of 13	NP_001317383.1	J3KNW5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLUAP1	ENST00000576634.6	TSL:1 MANE Select	c.5C>T	p.Ser2Phe	missense	Exon 1 of 12	ENSP00000460850.1	Q96AJ1-1
CLUAP1	ENST00000341633.9	TSL:5	c.5C>T	p.Ser2Phe	missense	Exon 1 of 13	ENSP00000344392.5	J3KNW5
CLUAP1	ENST00000969006.1		c.5C>T	p.Ser2Phe	missense	Exon 1 of 13	ENSP00000639065.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000434

AC:

AN:

230542

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000943

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1447222

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33296

American (AMR)

AF:

0.00

AC:

AN:

44130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.00

AC:

AN:

39364

South Asian (SAS)

AF:

0.00

AC:

AN:

84906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.00000812

AC:

AN:

1108942

Other (OTH)

AF:

0.00

AC:

AN:

59990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

-0.033

MutationAssessor

Pathogenic

3.0

PhyloP100

3.8

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.64

MutPred

0.48

Loss of phosphorylation at S2 (P = 0.0158)

MVP

0.88

MPC

0.33

ClinPred

1.0

GERP RS

4.9

PromoterAI

-0.093

Neutral

(source)

Varity_R

0.89

gMVP

0.88

Mutation Taster

=63/37

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over