18-633327-A-T

Position:

• chr18-633327-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.270

Genes affected

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

LOC105371952 (HGNC:):

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

ACMG classification

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/exons	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.886A>T	p.Met296Leu	missense_variant	7/10	ENST00000692774.1	NP_001380273.1
LOC105371952	XR_935082.4	n.3526-621T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.886A>T	p.Met296Leu	missense_variant	7/10		NM_001393344.1	ENSP00000510271	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

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	T
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	N
LIST_S2	Benign	0.49	.;.;T;T;.;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.039	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.;.;L;L
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.25	T
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	T
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.

Other links and lift over

hg19: chr18-633327;