19-51225311-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F44S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD33 NM_001772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• Publications: 7 publications found

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]

ENSG00000268595 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001772.4. 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
	CD33	NM_001772.4	MANE Select	c.131T>G	p.Phe44Cys	missense	Exon 2 of 7	NP_001763.3	Q546G0
	CD33	NM_001177608.2		c.131T>G	p.Phe44Cys	missense	Exon 2 of 7	NP_001171079.1	P20138-2
	CD33	NM_001082618.2		c.37+156T>G		intron	N/A	NP_001076087.1	P20138-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	ENST00000262262.5	TSL:1 MANE Select	c.131T>G	p.Phe44Cys	missense	Exon 2 of 7	ENSP00000262262.3	P20138-1
	CD33	ENST00000391796.7	TSL:1	c.131T>G	p.Phe44Cys	missense	Exon 2 of 7	ENSP00000375673.2	P20138-2
	CD33	ENST00000421133.6	TSL:1	c.37+156T>G		intron	N/A	ENSP00000410126.1	P20138-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.40
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.083
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.0090	B
Vest4		0.22
MutPred		0.58		Gain of sheet (P = 0.1451)
MVP		0.16
MPC		0.32
ClinPred		0.74	D
GERP RS		-7.3
PromoterAI		0.041	Neutral
Varity_R		0.31
gMVP		0.39
Mutation Taster		=70/30	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: rs61736469; hg19: chr19-51728567;