1-157833318-C-G

Variant names:

• chr1-157833318-C-G
• rs151280062
• NM_005894.3:c.913G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005894.3(CD5L):​c.913G>C​(p.Val305Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V305I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD5L NM_005894.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106821775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005894.3. 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
	CD5L	NM_005894.3	MANE Select	c.913G>C	p.Val305Leu	missense	Exon 5 of 6	NP_005885.1	O43866
	CD5L	NM_001347698.2		c.913G>C	p.Val305Leu	missense	Exon 5 of 6	NP_001334627.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD5L	ENST00000368174.5	TSL:1 MANE Select	c.913G>C	p.Val305Leu	missense	Exon 5 of 6	ENSP00000357156.4	O43866

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.2
DANN	Benign	0.94
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.37	N
PhyloP100		-2.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.064
Sift	Benign	0.51	T
Sift4G	Benign	0.41	T
Polyphen		0.34	B
Vest4		0.11
MutPred		0.60		Loss of MoRF binding (P = 0.1093)
MVP		0.28
MPC		0.32
ClinPred		0.16	T
GERP RS		0.81
Varity_R		0.049
gMVP		0.35
Mutation Taster		=100/0	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: rs151280062; hg19: chr1-157803108;