chr18-619282-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001393344.1(CLUL1):ā€‹c.176T>Cā€‹(p.Met59Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

CLUL1
NM_001393344.1 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10
Variant links:
Genes affected
CLUL1 (HGNC:2096): (clusterin like 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
CLUL1NM_001393344.1 linkuse as main transcriptc.176T>C p.Met59Thr missense_variant 4/10 ENST00000692774.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLUL1ENST00000692774.1 linkuse as main transcriptc.176T>C p.Met59Thr missense_variant 4/10 NM_001393344.1 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461736
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsAug 21, 2023The c.176T>C (p.M59T) alteration is located in exon 3 (coding exon 2) of the CLUL1 gene. This alteration results from a T to C substitution at nucleotide position 176, causing the methionine (M) at amino acid position 59 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
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
.;T;T;.;T;T;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.82
T;.;.;T;T;.;T
M_CAP
Benign
0.023
T
MetaRNN
Pathogenic
0.80
D;D;D;D;D;D;D
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.6
.;M;.;.;.;M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-4.8
.;D;D;.;.;D;.
REVEL
Uncertain
0.44
Sift
Uncertain
0.0070
.;D;D;.;.;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0, 1.0
.;D;D;.;D;D;D
Vest4
0.86, 0.83, 0.84, 0.83, 0.86
MutPred
0.71
.;.;Gain of methylation at K112 (P = 0.0438);.;Gain of methylation at K112 (P = 0.0438);.;.;
MVP
0.27
MPC
0.91
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.74
gMVP
0.64

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.

Other links and lift over

hg19: chr18-619282; API