12-7485102-A-T

Variant names:

• chr12-7485102-A-T
• NM_203416.4:c.2773T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_203416.4(CD163):​c.2773T>A​(p.Cys925Ser) variant causes a missense change. 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: CD163 NM_203416.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75

Genes affected

CD163 (HGNC:1631): (CD163 molecule) The protein encoded by this gene is a member of the scavenger receptor cysteine-rich (SRCR) superfamily, and is exclusively expressed in monocytes and macrophages. It functions as an acute phase-regulated receptor involved in the clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages, and may thereby protect tissues from free hemoglobin-mediated oxidative damage. This protein may also function as an innate immune sensor for bacteria and inducer of local inflammation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD163	NM_203416.4	c.2773T>A	p.Cys925Ser	missense_variant	Exon 11 of 17	ENST00000432237.3	NP_981961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD163	ENST00000432237.3	c.2773T>A	p.Cys925Ser	missense_variant	Exon 11 of 17	1	NM_203416.4	ENSP00000403885.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2773T>A (p.C925S) alteration is located in exon 11 (coding exon 11) of the CD163 gene. This alteration results from a T to A substitution at nucleotide position 2773, causing the cysteine (C) at amino acid position 925 to be replaced by a serine (S). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T;.;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.98	D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.0	H;.;.;H
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.6	D;D;D;D
REVEL	Pathogenic	0.81
Sift	Benign	0.062	T;T;T;T
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.87
MutPred		0.87		Gain of disorder (P = 0.0067);.;.;Gain of disorder (P = 0.0067);
MVP		0.97
MPC		1.5
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.91
gMVP		0.93

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: chr12-7637698;