19-51225311-T-G

Variant names:

• chr19-51225311-T-G
• rs61736469
• NM_001772.4:c.131T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001772.4(CD33):​c.131T>G​(p.Phe44Cys) 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: -0.396

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13501036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4	c.131T>G	p.Phe44Cys	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.131T>G	p.Phe44Cys	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	0.30
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.0
DANN	Benign	0.48
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.083
Sift	Benign	0.17	T;D
Sift4G	Benign	0.15	T;T
Polyphen		0.0090	.;B
Vest4		0.22
MutPred		0.58		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.16
MPC		0.32
ClinPred		0.74	D
GERP RS		-7.3
Varity_R		0.31
gMVP		0.39

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: rs61736469; hg19: chr19-51728567;