19-51225365-G-T

Variant names:

• chr19-51225365-G-T
• rs144102805
• NM_001772.4:c.185G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001772.4(CD33):​c.185G>T​(p.Arg62Leu) 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. 13/21 in silico tools predict a benign 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: CD33 NM_001772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

Genes affected

CD33 (HGNC:1659): (CD33 molecule) Enables protein phosphatase binding activity and sialic acid binding activity. Involved in several processes, including negative regulation of cytokine production; negative regulation of monocyte activation; and positive regulation of protein tyrosine phosphatase activity. Located in several cellular components, including Golgi apparatus; external side of plasma membrane; and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985327 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36959434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4	c.185G>T	p.Arg62Leu	missense_variant	Exon 2 of 7	ENST00000262262.5	NP_001763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD33	ENST00000262262.5	c.185G>T	p.Arg62Leu	missense_variant	Exon 2 of 7	1	NM_001772.4	ENSP00000262262.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.32	.;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.37
Sift	Benign	0.11	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.70	.;P
Vest4		0.14
MutPred		0.71		Gain of catalytic residue at F61 (P = 0.1843);Gain of catalytic residue at F61 (P = 0.1843);
MVP		0.79
MPC		0.20
ClinPred		0.81	D
GERP RS		-5.2
Varity_R		0.33
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs144102805; hg19: chr19-51728621; COSMIC: COSV51803658; COSMIC: COSV51803658;