NM_174941.6:c.4252G>C

Variant names:

• chr12-7367263-C-G
• NM_174941.6:c.4252G>C

Variant summary

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

The NM_174941.6(CD163L1):​c.4252G>C​(p.Glu1418Gln) 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: CD163L1 NM_174941.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

CD163L1 (HGNC:30375): (CD163 molecule like 1) This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. The SRCR family is defined by a 100-110 amino acid SRCR domain, which may mediate protein-protein interaction and ligand binding. The encoded protein contains twelve SRCR domains, a transmembrane region and a cytoplasmic domain. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

CD163L1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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=0.10150987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174941.6. 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
	CD163L1	NM_174941.6	MANE Select	c.4252G>C	p.Glu1418Gln	missense	Exon 18 of 20	NP_777601.3	Q9NR16-1
	CD163L1	NM_001297650.2		c.4282G>C	p.Glu1428Gln	missense	Exon 18 of 20	NP_001284579.2	Q9NR16-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD163L1	ENST00000313599.8	TSL:1 MANE Select	c.4252G>C	p.Glu1418Gln	missense	Exon 18 of 20	ENSP00000315945.3	Q9NR16-1
	CD163L1	ENST00000416109.2	TSL:2	c.4282G>C	p.Glu1428Gln	missense	Exon 18 of 20	ENSP00000393474.2	Q9NR16-4
	CD163L1	ENST00000539726.5	TSL:5	c.217G>C	p.Glu73Gln	missense	Exon 3 of 5	ENSP00000438217.1	H0YFE6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.088
Sift	Benign	0.035	D
Sift4G	Benign	0.099	T
Polyphen		0.99	D
Vest4		0.068
MutPred		0.25		Gain of catalytic residue at L1415 (P = 0.0022)
MVP		0.46
MPC		0.59
ClinPred		0.15	T
GERP RS		1.9
Varity_R		0.056
gMVP		0.39
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr12-7519859;