18-627251-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001393344.1(CLUL1):​c.578C>T​(p.Ser193Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S193C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLUL1 NM_001393344.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

Genes affected

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

LOC105371952 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06162566).

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>T	p.Ser193Phe	missense	Exon 6 of 10	NP_001380273.1	Q15846
	CLUL1	NM_001289036.3		c.578C>T	p.Ser193Phe	missense	Exon 7 of 11	NP_001275965.2	Q15846
	CLUL1	NM_001318522.2		c.578C>T	p.Ser193Phe	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>T	p.Ser193Phe	missense	Exon 6 of 10	ENSP00000510271.1	Q15846
	CLUL1	ENST00000338387.11	TSL:1	c.578C>T	p.Ser193Phe	missense	Exon 5 of 9	ENSP00000341128.6	Q15846
	CLUL1	ENST00000400606.6	TSL:1	c.578C>T	p.Ser193Phe	missense	Exon 5 of 9	ENSP00000383449.2	Q15846

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 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: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.12
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.095	N
PhyloP100		1.7
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.075
Sift	Benign	0.41	T
Sift4G	Benign	0.18	T
Polyphen		0.012	B
Vest4		0.17
MutPred		0.51		Loss of disorder (P = 0.046)
MVP		0.040
MPC		0.26
ClinPred		0.055	T
GERP RS		2.6
Varity_R		0.062
gMVP		0.28
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: COSV58111821; COSMIC: COSV58111821;