Genetic Variant CD5L:p.Asp54Tyr (chr1-157836051-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005894.3(CD5L):c.160G>T(p.Asp54Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,614,046 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

CD5L
NM_005894.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD5L	NM_005894.3 link	c.160G>T	p.Asp54Tyr	missense_variant	Exon 3 of 6	ENST00000368174.5	NP_005885.1	O43866
CD5L	NM_001347698.2 link	c.160G>T	p.Asp54Tyr	missense_variant	Exon 3 of 6		NP_001334627.1	O43866
CD5L	XM_017002806.2 link	c.160G>T	p.Asp54Tyr	missense_variant	Exon 3 of 6		XP_016858295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD5L	ENST00000368174.5 link	c.160G>T	p.Asp54Tyr	missense_variant	Exon 3 of 6	1	NM_005894.3	ENSP00000357156.4		O43866
CD5L	ENST00000484609.1 link	n.397G>T		non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152186

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:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251380

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135852

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:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

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:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.160G>T (p.D54Y) alteration is located in exon 3 (coding exon 3) of the CD5L gene. This alteration results from a G to T substitution at nucleotide position 160, causing the aspartic acid (D) at amino acid position 54 to be replaced by a tyrosine (Y). 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Benign

0.090

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.78

M_CAP

Benign

0.036

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.2

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.60

MutPred

0.72

Gain of ubiquitination at K56 (P = 0.1162);

MVP

0.64

MPC

0.91

ClinPred

0.78

GERP RS

-0.54

Varity_R

0.71

gMVP

0.75

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

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