19-51225535-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1

The NM_001772.4(CD33):​c.355C>T​(p.Arg119Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,599,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.24

Publications

2 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity CD33_HUMAN

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD33NM_001772.4 linkc.355C>T p.Arg119Trp 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.355C>T p.Arg119Trp missense_variant Exon 2 of 7 1 NM_001772.4 ENSP00000262262.3 P20138-1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152136
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000591
AC:
14
AN:
237062
AF XY:
0.0000625
show subpopulations
Gnomad AFR exome
AF:
0.0000631
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000121
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000155
AC:
225
AN:
1447154
Hom.:
0
Cov.:
33
AF XY:
0.000149
AC XY:
107
AN XY:
718810
show subpopulations
African (AFR)
AF:
0.0000303
AC:
1
AN:
33032
American (AMR)
AF:
0.00
AC:
0
AN:
43272
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24756
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39598
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83874
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52690
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
0.000196
AC:
216
AN:
1104528
Other (OTH)
AF:
0.000134
AC:
8
AN:
59726
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
14
29
43
58
72
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152136
Hom.:
0
Cov.:
31
AF XY:
0.000135
AC XY:
10
AN XY:
74328
show subpopulations
African (AFR)
AF:
0.0000724
AC:
3
AN:
41422
American (AMR)
AF:
0.00
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000206
AC:
14
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.531
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000152
Hom.:
0
Bravo
AF:
0.000147
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 01, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.355C>T (p.R119W) alteration is located in exon 2 (coding exon 2) of the CD33 gene. This alteration results from a C to T substitution at nucleotide position 355, causing the arginine (R) at amino acid position 119 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
12
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
.;D
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.60
D;D
MetaSVM
Benign
-0.64
T
MutationAssessor
Pathogenic
3.2
M;M
PhyloP100
-2.2
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Uncertain
0.36
Sift
Benign
0.036
D;T
Sift4G
Uncertain
0.044
D;D
Polyphen
0.99
.;D
Vest4
0.49
MVP
0.84
MPC
0.28
ClinPred
0.65
D
GERP RS
-1.8
PromoterAI
-0.050
Neutral
Varity_R
0.38
gMVP
0.46
Mutation Taster
=78/22
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

Publications

Other links and lift over

dbSNP: rs202143203; hg19: chr19-51728791; COSMIC: COSV51803787; COSMIC: COSV51803787; API