18-627328-T-C

Position:

• chr18-627328-T-C

Variant summary

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

The NM_001393344.1(CLUL1):​c.655T>C​(p.Ser219Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.62

Genes affected

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

LOC105371952 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.655T>C	p.Ser219Pro	missense_variant	6/10	ENST00000692774.1	NP_001380273.1
LOC105371952	XR_935082.4	n.3675-2582A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.655T>C	p.Ser219Pro	missense_variant	6/10		NM_001393344.1	ENSP00000510271	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

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

Sep 26, 2022

The c.655T>C (p.S219P) alteration is located in exon 5 (coding exon 4) of the CLUL1 gene. This alteration results from a T to C substitution at nucleotide position 655, causing the serine (S) at amino acid position 219 to be replaced by a proline (P). 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	0.20
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;T;.;T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	.;.;T;T;.;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.63	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.;.;.;M;M
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N;N;.;.;N;.
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D;.;.;D;.
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		1.0	D;D;.;D;D;D
Vest4		0.77
MutPred		0.46		.;Loss of stability (P = 0.0209);.;Loss of stability (P = 0.0209);.;.;
MVP		0.030
MPC		0.94
ClinPred		0.95	D
GERP RS		5.9
Varity_R		0.58
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: chr18-627328;