12-7369385-G-T

Variant names:

• chr12-7369385-G-T
• rs1265932307
• NM_174941.6:c.4011C>A

Variant summary

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

The NM_174941.6(CD163L1):​c.4011C>A​(p.His1337Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD163L1 NM_174941.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4011C>A	p.His1337Gln	missense	Exon 15 of 20	NP_777601.3	Q9NR16-1
	CD163L1	NM_001297650.2		c.4041C>A	p.His1347Gln	missense	Exon 15 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.4011C>A	p.His1337Gln	missense	Exon 15 of 20	ENSP00000315945.3	Q9NR16-1
	CD163L1	ENST00000416109.2	TSL:2	c.4041C>A	p.His1347Gln	missense	Exon 15 of 20	ENSP00000393474.2	Q9NR16-4
	CD163L1	ENST00000878199.1		c.4041C>A	p.His1347Gln	missense	Exon 15 of 19	ENSP00000548258.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0030	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		0.59
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.76		Gain of catalytic residue at A1341 (P = 0.0258)
MVP		0.58
MPC		0.82
ClinPred		0.69	D
GERP RS		0.65
PromoterAI		0.064	Neutral
Varity_R		0.72
gMVP		0.65
Mutation Taster		=96/4	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: rs1265932307; hg19: chr12-7521981;