19-51225452-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001772.4(CD33):​c.272G>A​(p.Arg91His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.988
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.037290305).
BP6
Variant 19-51225452-G-A is Benign according to our data. Variant chr19-51225452-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3488053.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD33NM_001772.4 linkc.272G>A p.Arg91His missense_variant Exon 2 of 7 ENST00000262262.5 NP_001763.3 P20138-1Q546G0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD33ENST00000262262.5 linkc.272G>A p.Arg91His missense_variant Exon 2 of 7 1 NM_001772.4 ENSP00000262262.3 P20138-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152178
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251176
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461766
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152296
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 29, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.060
DANN
Benign
0.10
DEOGEN2
Benign
0.063
.;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.0060
N
LIST_S2
Benign
0.25
T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.037
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.1
N;N
PrimateAI
Benign
0.18
T
PROVEAN
Benign
5.2
N;N
REVEL
Benign
0.11
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
.;B
Vest4
0.024
MutPred
0.68
Loss of disorder (P = 0.0633);Loss of disorder (P = 0.0633);
MVP
0.55
MPC
0.079
ClinPred
0.018
T
GERP RS
-7.0
Varity_R
0.14
gMVP
0.13

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs555362730; hg19: chr19-51728708; API