Genetic Variant CD5L:p.Glu237Lys (chr1-157834416-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005894.3(CD5L):c.709G>A(p.Glu237Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CD5L
NM_005894.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.550

Variant links:

Genes affected

CD5L (HGNC:1690): (CD5 molecule like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Predicted to act upstream of or within positive regulation of complement-dependent cytotoxicity and regulation of complement activation. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

CD5L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.23246118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD5L	NM_005894.3 link	c.709G>A	p.Glu237Lys	missense_variant	Exon 4 of 6	ENST00000368174.5	NP_005885.1	O43866
CD5L	NM_001347698.2 link	c.709G>A	p.Glu237Lys	missense_variant	Exon 4 of 6		NP_001334627.1	O43866
CD5L	XM_017002806.2 link	c.709G>A	p.Glu237Lys	missense_variant	Exon 4 of 6		XP_016858295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD5L	ENST00000368174.5 link	c.709G>A	p.Glu237Lys	missense_variant	Exon 4 of 6	1	NM_005894.3	ENSP00000357156.4		O43866

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248110

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1458922

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.709G>A (p.E237K) alteration is located in exon 4 (coding exon 4) of the CD5L gene. This alteration results from a G to A substitution at nucleotide position 709, causing the glutamic acid (E) at amino acid position 237 to be replaced by a lysine (K). 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

0.26

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.094

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.59

M_CAP

Benign

0.0084

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.6

REVEL

Benign

0.038

Sift

Benign

0.14

Sift4G

Benign

0.084

Polyphen

0.96

Vest4

0.11

MVP

0.37

MPC

0.26

ClinPred

0.30

GERP RS

2.1

Varity_R

0.041

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over