chr19-51225221-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001772.4(CD33):c.41C>T(p.Ala14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,612,814 control chromosomes in the GnomAD database, including 79,734 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.25 ( 6052 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73682 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.191

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]

CD33 links:

LOC107985327 (HGNC:):

LOC107985327 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2751093E-4).

BP6

Variant 19-51225221-C-T is Benign according to our data. Variant chr19-51225221-C-T is described in ClinVar as [Benign]. Clinvar id is 1275129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4 link	c.41C>T	p.Ala14Val	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
CD33	ENST00000262262.5 link	c.41C>T	p.Ala14Val	missense_variant	Exon 2 of 7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38597

AN:

152014

Hom.:

6040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0872

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.307

AC:

76894

AN:

250170

Hom.:

14417

AF XY:

0.294

AC XY:

39783

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.0800

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.320

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.307

AC:

448224

AN:

1460682

Hom.:

73682

Cov.:

AF XY:

0.301

AC XY:

218666

AN XY:

726522

show subpopulations

Gnomad4 AFR exome

AF:

0.0756

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.254

AC:

38618

AN:

152132

Hom.:

6052

Cov.:

AF XY:

0.258

AC XY:

19208

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0871

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.260

Hom.:

3374

Bravo

AF:

0.255

TwinsUK

AF:

0.324

AC:

1200

ALSPAC

AF:

0.336

AC:

1296

ESP6500AA

AF:

0.0933

AC:

411

ESP6500EA

AF:

0.301

AC:

2585

ExAC

AF:

0.293

AC:

35573

Asia WGS

AF:

0.169

AC:

591

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.299

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25762156, 24381305, 26621708, 23946390, 30917570) -

Mar 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

.;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.00023

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.043

Sift

Uncertain

0.029

D;T

Sift4G

Benign

0.13

T;T

Polyphen

0.48

.;P

Vest4

0.057

MPC

0.097

ClinPred

0.014

GERP RS

0.92

Varity_R

0.031

gMVP

0.31

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over