Variant 18-633327-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001393344.1(CLUL1):c.886A>T(p.Met296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CLUL1
NM_001393344.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.270

Variant links:

Genes affected

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

CLUL1 links:

TYMSOS (HGNC:29553): (TYMS opposite strand RNA)

TYMSOS links:

LOC105371952 (HGNC:):

LOC105371952 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038959235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLUL1	NM_001393344.1 link	c.886A>T	p.Met296Leu	missense_variant	Exon 7 of 10	ENST00000692774.1	NP_001380273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1 link	c.886A>T	p.Met296Leu	missense_variant	Exon 7 of 10		NM_001393344.1	ENSP00000510271.1		Q15846

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Jan 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.886A>T (p.M296L) alteration is located in exon 6 (coding exon 5) of the CLUL1 gene. This alteration results from a A to T substitution at nucleotide position 886, causing the methionine (M) at amino acid position 296 to be replaced by a leucine (L). 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

0.089

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.0

DANN

Benign

0.39

DEOGEN2

Benign

0.0010

T;T;.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.49

.;.;T;T;.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.039

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.;L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.46

N;N;.;.;N;.

REVEL

Benign

0.091

Sift

Benign

1.0

T;T;.;.;T;.

Sift4G

Benign

0.91

T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;B;B

Vest4

0.14

MutPred

0.49

.;Gain of methylation at K347 (P = 0.0391);.;Gain of methylation at K347 (P = 0.0391);.;.;

MVP

0.014

MPC

0.21

ClinPred

0.052

GERP RS

-0.26

Varity_R

0.094

gMVP

0.13

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over