1-157835951-T-C

Variant names:

• chr1-157835951-T-C
• NM_005894.3:c.260A>G

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.260A>G​(p.Gln87Arg) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD5L NM_005894.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0450
• Publications: 0 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=0.19985938).

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.260A>G	p.Gln87Arg	missense	Exon 3 of 6	NP_005885.1	O43866
	CD5L	NM_001347698.2		c.260A>G	p.Gln87Arg	missense	Exon 3 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.260A>G	p.Gln87Arg	missense	Exon 3 of 6	ENSP00000357156.4	O43866
	CD5L	ENST00000484609.1	TSL:5	n.497A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.045
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.031
Sift	Benign	0.068	T
Sift4G	Benign	0.47	T
Polyphen		0.075	B
Vest4		0.082
MutPred		0.72		Gain of sheet (P = 0.0827)
MVP		0.45
MPC		0.42
ClinPred		0.12	T
GERP RS		2.2
Varity_R		0.23
gMVP		0.63
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

hg19: chr1-157805741;