18-644932-G-A

Position:

• chr18-644932-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393344.1(CLUL1):​c.1232G>A​(p.Gly411Glu) 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: 0.711

Genes affected

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

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

LOC105371952 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082828075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.1232G>A	p.Gly411Glu	missense_variant	9/10	ENST00000692774.1	NP_001380273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.1232G>A	p.Gly411Glu	missense_variant	9/10		NM_001393344.1	ENSP00000510271.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jul 30, 2024

The c.1232G>A (p.G411E) alteration is located in exon 8 (coding exon 7) of the CLUL1 gene. This alteration results from a G to A substitution at nucleotide position 1232, causing the glycine (G) at amino acid position 411 to be replaced by a glutamic acid (E). 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	0.065
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.8
DANN	Benign	0.84
DEOGEN2	Benign	0.0035	T;T;.;T;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.66	.;.;T;T;.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.083	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;.;.;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.5	N;N;.;.;N;.
REVEL	Benign	0.021
Sift	Benign	0.13	T;T;.;.;T;.
Sift4G	Benign	0.32	T;T;T;T;T;T
Polyphen		0.30	B;P;.;P;B;B
Vest4		0.18
MutPred		0.33		.;Gain of solvent accessibility (P = 0.012);.;Gain of solvent accessibility (P = 0.012);.;.;
MVP		0.030
MPC		0.31
ClinPred		0.31	T
GERP RS		1.0
Varity_R		0.068
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-644932;