Variant 18-618061-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001393344.1(CLUL1):c.61G>A(p.Ala21Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CLUL1
NM_001393344.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Variant links:

Genes affected

CLUL1 (HGNC:2096): (clusterin like 1)

CLUL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.270832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLUL1	NM_001393344.1 linkuse as main transcript	c.61G>A	p.Ala21Thr	missense_variant	3/10	ENST00000692774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLUL1	ENST00000692774.1 linkuse as main transcript	c.61G>A	p.Ala21Thr	missense_variant	3/10		NM_001393344.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249500

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000290

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000248

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.61G>A (p.A21T) alteration is located in exon 2 (coding exon 1) of the CLUL1 gene. This alteration results from a G to A substitution at nucleotide position 61, causing the alanine (A) at amino acid position 21 to be replaced by a threonine (T). 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

Benign

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.026

.;T;T;.;T;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

T;.;.;T;T;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.27

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M;.;.;.;M;M

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

.;N;N;.;.;N;.

REVEL

Benign

0.20

Sift

Uncertain

0.0080

.;D;D;.;.;D;.

Sift4G

Uncertain

0.019

D;D;D;D;D;D;D

Polyphen

1.0

.;D;D;.;D;D;D

Vest4

0.51, 0.63, 0.54, 0.63, 0.51

MutPred

0.67

.;.;Gain of phosphorylation at A73 (P = 0.0744);.;Gain of phosphorylation at A73 (P = 0.0744);.;.;

MVP

0.088

MPC

0.83

ClinPred

0.66

GERP RS

4.8

Varity_R

0.14

gMVP

0.16

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

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