chr18-627200-A-G

Position:

• chr18-627200-A-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.527A>G​(p.Gln176Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CLUL1 NM_001393344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.01

Genes affected

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

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=0.16085204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.527A>G	p.Gln176Arg	missense_variant	6/10	ENST00000692774.1	NP_001380273.1
LOC105371952	XR_935082.4	n.3675-2454T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.527A>G	p.Gln176Arg	missense_variant	6/10		NM_001393344.1	ENSP00000510271	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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 16, 2024

The c.527A>G (p.Q176R) alteration is located in exon 5 (coding exon 4) of the CLUL1 gene. This alteration results from a A to G substitution at nucleotide position 527, causing the glutamine (Q) at amino acid position 176 to be replaced by an arginine (R). 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	0.083
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	T;T;.;T;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.52	.;.;T;T;.;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;.;.;M;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N;N;.;.;N;.
REVEL	Benign	0.070
Sift	Uncertain	0.0060	D;T;.;.;D;.
Sift4G	Uncertain	0.015	D;D;D;D;D;D
Polyphen		0.15	B;P;.;P;B;B
Vest4		0.23
MutPred		0.47		.;Gain of phosphorylation at T230 (P = 0.0966);.;Gain of phosphorylation at T230 (P = 0.0966);.;.;
MVP		0.22
MPC		0.36
ClinPred		0.76	D
GERP RS		3.2
Varity_R		0.14
gMVP		0.46

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: chr18-627200;