chr18-641341-C-A

Variant names:

• chr18-641341-C-A
• NM_001393344.1:c.1009C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393344.1(CLUL1):​c.1009C>A​(p.Pro337Thr) 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 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLUL1 NM_001393344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

Genes affected

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

TYMSOS (HGNC:29553): (TYMS opposite strand RNA)

LOC105371952 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3207417).

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.1009C>A	p.Pro337Thr	missense	Exon 8 of 10	NP_001380273.1	Q15846
	CLUL1	NM_001289036.3		c.1009C>A	p.Pro337Thr	missense	Exon 9 of 11	NP_001275965.2	Q15846
	CLUL1	NM_001318522.2		c.1009C>A	p.Pro337Thr	missense	Exon 7 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.1009C>A	p.Pro337Thr	missense	Exon 8 of 10	ENSP00000510271.1	Q15846
	CLUL1	ENST00000338387.11	TSL:1	c.1009C>A	p.Pro337Thr	missense	Exon 7 of 9	ENSP00000341128.6	Q15846
	CLUL1	ENST00000400606.6	TSL:1	c.1009C>A	p.Pro337Thr	missense	Exon 7 of 9	ENSP00000383449.2	Q15846

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

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

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.010
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.8
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.18
Sift	Benign	0.034	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.33		Gain of phosphorylation at P389 (P = 0.08)
MVP		0.13
MPC		0.82
ClinPred		0.93	D
GERP RS		3.8
PromoterAI		0.032	Neutral
Varity_R		0.094
gMVP		0.20
Mutation Taster		=91/9	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

hg19: chr18-641341;