Variant 4-15834223-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001775.4(CD38):c.506A>G(p.Asn169Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,448,322 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CD38
NM_001775.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Variant links:

Genes affected

CD38 (HGNC:1667): (CD38 molecule) The protein encoded by this gene is a non-lineage-restricted, type II transmembrane glycoprotein that synthesizes and hydrolyzes cyclic adenosine 5'-diphosphate-ribose, an intracellular calcium ion mobilizing messenger. The release of soluble protein and the ability of membrane-bound protein to become internalized indicate both extracellular and intracellular functions for the protein. This protein has an N-terminal cytoplasmic tail, a single membrane-spanning domain, and a C-terminal extracellular region with four N-glycosylation sites. Crystal structure analysis demonstrates that the functional molecule is a dimer, with the central portion containing the catalytic site. It is used as a prognostic marker for patients with chronic lymphocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

CD38 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD38	NM_001775.4 linkuse as main transcript	c.506A>G	p.Asn169Ser	missense_variant	4/8	ENST00000226279.8	NP_001766.2	P28907-1B4E006
CD38	NR_132660.2 linkuse as main transcript	n.457A>G		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD38	ENST00000226279.8 linkuse as main transcript	c.506A>G	p.Asn169Ser	missense_variant	4/8	1	NM_001775.4	ENSP00000226279.2	P28907-1
CD38	ENST00000502843.5 linkuse as main transcript	n.*1A>G		non_coding_transcript_exon_variant	3/7	1		ENSP00000427277.1	P28907-2
CD38	ENST00000502843.5 linkuse as main transcript	n.*1A>G		3_prime_UTR_variant	3/7	1		ENSP00000427277.1	P28907-2
CD38	ENST00000510674.1 linkuse as main transcript	c.170A>G	p.Asn57Ser	missense_variant	3/6	5		ENSP00000423047.1	H0Y950

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251350

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448322

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721630

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.506A>G (p.N169S) alteration is located in exon 4 (coding exon 4) of the CD38 gene. This alteration results from a A to G substitution at nucleotide position 506, causing the asparagine (N) at amino acid position 169 to be replaced by a serine (S). 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

0.18

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.62

T;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.26

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.98

D;.

Vest4

0.49

MutPred

0.72

Loss of stability (P = 0.0793);.;

MVP

0.42

MPC

0.72

ClinPred

0.90

GERP RS

5.4

Varity_R

0.24

gMVP

0.45

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