12-7369645-C-T

Position:

• chr12-7369645-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_174941.6(CD163L1):​c.3751G>A​(p.Gly1251Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD163L1 NM_174941.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.887

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD163L1	NM_174941.6	c.3751G>A	p.Gly1251Arg	missense_variant	15/20	ENST00000313599.8	NP_777601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD163L1	ENST00000313599.8	c.3751G>A	p.Gly1251Arg	missense_variant	15/20	1	NM_174941.6	ENSP00000315945.3
CD163L1	ENST00000416109.2	c.3781G>A	p.Gly1261Arg	missense_variant	15/20	2		ENSP00000393474.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.3751G>A (p.G1251R) alteration is located in exon 15 (coding exon 15) of the CD163L1 gene. This alteration results from a G to A substitution at nucleotide position 3751, causing the glycine (G) at amino acid position 1251 to be replaced by an arginine (R). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.00024	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T;.
Eigen	Benign	0.026
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	4.3	H;.
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;.
Vest4		0.22
MutPred		0.84		Gain of MoRF binding (P = 0.0243);.;
MVP		0.79
MPC		0.90
ClinPred		1.0	D
GERP RS		1.4
Varity_R		0.56
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-7522241;