chr19-51225221-C-G

Variant names:

• chr19-51225221-C-G
• rs12459419
• NM_001772.4:c.41C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000262262.5(CD33):​c.41C>G​(p.Ala14Gly) 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. 16/22 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. A14V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD33 ENST00000262262.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 162 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=0.10556179).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262262.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	NM_001772.4	MANE Select	c.41C>G	p.Ala14Gly	missense	Exon 2 of 7	NP_001763.3
	CD33	NM_001177608.2		c.41C>G	p.Ala14Gly	missense	Exon 2 of 7	NP_001171079.1
	CD33	NM_001082618.2		c.37+66C>G		intron	N/A	NP_001076087.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	ENST00000262262.5	TSL:1 MANE Select	c.41C>G	p.Ala14Gly	missense	Exon 2 of 7	ENSP00000262262.3
	CD33	ENST00000391796.7	TSL:1	c.41C>G	p.Ala14Gly	missense	Exon 2 of 7	ENSP00000375673.2
	CD33	ENST00000421133.6	TSL:1	c.37+66C>G		intron	N/A	ENSP00000410126.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 5561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.19
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.021
Sift	Benign	0.063	T
Sift4G	Benign	0.082	T
Polyphen		0.0030	B
Vest4		0.15
MutPred		0.48		Gain of sheet (P = 0.0477)
MVP		0.24
MPC		0.066
ClinPred		0.059	T
GERP RS		0.92
PromoterAI		0.011	Neutral
Varity_R		0.038
gMVP		0.25
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12459419; hg19: chr19-51728477;