Variant NM_001772.4:c.131T>C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001772.4(CD33):c.131T>C(p.Phe44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,614,156 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 7 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.396

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=0.0026769042).

BP6

Variant 19-51225311-T-C is Benign according to our data. Variant chr19-51225311-T-C is described in ClinVar as [Benign]. Clinvar id is 777507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00818 (1245/152282) while in subpopulation AFR AF= 0.0276 (1148/41542). AF 95% confidence interval is 0.0263. There are 15 homozygotes in gnomad4. There are 606 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4 link	c.131T>C	p.Phe44Ser	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.131T>C	p.Phe44Ser	missense_variant	Exon 2 of 7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.00818

AC:

1244

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00224

AC:

563

AN:

251468

Hom.:

AF XY:

0.00189

AC XY:

257

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0260

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000900

AC:

1315

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000815

AC XY:

593

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00818

AC:

1245

AN:

152282

Hom.:

Cov.:

AF XY:

0.00814

AC XY:

606

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00912

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0261

AC:

115

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00270

AC:

328

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.41

DANN

Benign

0.26

DEOGEN2

Benign

0.069

.;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.027

T;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.89

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.034

Sift

Benign

0.96

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.062

MVP

0.14

MPC

0.11

ClinPred

0.00070

GERP RS

-7.3

Varity_R

0.16

gMVP

0.27

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

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