19-51225221-C-A

Position:

• chr19-51225221-C-A

Variant summary

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

The NM_001772.4(CD33):​c.41C>A​(p.Ala14Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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 NM_001772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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=0.14651853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD33	NM_001772.4	c.41C>A	p.Ala14Asp	missense_variant	2/7	ENST00000262262.5
LOC107985327	XR_007067309.1	n.232-30561G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD33	ENST00000262262.5	c.41C>A	p.Ala14Asp	missense_variant	2/7	1	NM_001772.4	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.042	.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.054
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		0.48	.;P
Vest4		0.19
MutPred		0.56		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.31
MPC		0.20
ClinPred		0.20	T
GERP RS		0.92
Varity_R		0.097
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12459419; hg19: chr19-51728477; COSMIC: COSV105094373; COSMIC: COSV105094373;