chr18-625004-A-G

Variant names:

• chr18-625004-A-G
• rs368036645
• NM_001393344.1:c.395A>G

Variant summary

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

The NM_001393344.1(CLUL1):​c.395A>G​(p.Gln132Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLUL1 NM_001393344.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693

Genes affected

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

ENSG00000288533 (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=0.0759058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.395A>G	p.Gln132Arg	missense_variant	Exon 5 of 10	ENST00000692774.1	NP_001380273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.395A>G	p.Gln132Arg	missense_variant	Exon 5 of 10		NM_001393344.1	ENSP00000510271.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.7
DANN	Benign	0.22
DEOGEN2	Benign	0.0016	T;T;.;T;T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.56	.;.;T;T;.;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.076	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;.;.;.;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.34	N;N;.;.;N;.
REVEL	Benign	0.038
Sift	Benign	0.89	T;T;.;.;T;.
Sift4G	Benign	0.32	T;T;T;T;T;T
Polyphen		0.11	B;B;.;B;B;B
Vest4		0.31
MutPred		0.52		.;Gain of MoRF binding (P = 0.0178);.;Gain of MoRF binding (P = 0.0178);.;.;
MVP		0.16
MPC		0.80
ClinPred		0.079	T
GERP RS		0.35
Varity_R		0.040
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs368036645; hg19: chr18-625004;