rs753466551

Variant names:

• chr18-627251-C-G
• rs753466551
• NM_001393344.1:c.578C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-627251-C-G
• chr18-627251-C-A
• chr18-627251-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393344.1(CLUL1):​c.578C>G​(p.Ser193Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S193T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CLUL1 NM_001393344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• Publications: 7 publications found

Genes affected

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

LOC105371952 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.080557644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393344.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUL1	NM_001393344.1	MANE Select	c.578C>G	p.Ser193Cys	missense	Exon 6 of 10	NP_001380273.1	Q15846
	CLUL1	NM_001289036.3		c.578C>G	p.Ser193Cys	missense	Exon 7 of 11	NP_001275965.2	Q15846
	CLUL1	NM_001318522.2		c.578C>G	p.Ser193Cys	missense	Exon 5 of 9	NP_001305451.1	Q15846

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLUL1	ENST00000692774.1	MANE Select	c.578C>G	p.Ser193Cys	missense	Exon 6 of 10	ENSP00000510271.1	Q15846
	CLUL1	ENST00000338387.11	TSL:1	c.578C>G	p.Ser193Cys	missense	Exon 5 of 9	ENSP00000341128.6	Q15846
	CLUL1	ENST00000400606.6	TSL:1	c.578C>G	p.Ser193Cys	missense	Exon 5 of 9	ENSP00000383449.2	Q15846

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152044 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249558 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461850 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727226

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111992

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152044 Hom.: 0 Cov.: 30 AF XY: 0.0000673 AC XY: 5 AN XY: 74244

African (AFR) AF: 0.000266 AC: 11 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.60
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.024
Sift	Benign	0.10	T
Sift4G	Benign	0.078	T
Polyphen		0.063	B
Vest4		0.21
MVP		0.061
MPC		0.25
ClinPred		0.033	T
GERP RS		2.6
Varity_R		0.086
gMVP		0.21
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs753466551; hg19: chr18-627251; COSMIC: COSV100621034; COSMIC: COSV100621034;