4-15840487-A-T

Variant names:

• chr4-15840487-A-T
• NM_001775.4:c.788A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001775.4(CD38):​c.788A>T​(p.Glu263Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD38 NM_001775.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.456

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4101529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4	c.788A>T	p.Glu263Val	missense_variant	Exon 7 of 8	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.739A>T		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.788A>T	p.Glu263Val	missense_variant	Exon 7 of 8	1	NM_001775.4	ENSP00000226279.2
CD38	ENST00000502843.5	n.*283A>T		non_coding_transcript_exon_variant	Exon 6 of 7	1		ENSP00000427277.1
CD38	ENST00000502843.5	n.*283A>T		3_prime_UTR_variant	Exon 6 of 7	1		ENSP00000427277.1
CD38	ENST00000510674.1	c.452A>T	p.Glu151Val	missense_variant	Exon 6 of 6	5		ENSP00000423047.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.788A>T (p.E263V) alteration is located in exon 7 (coding exon 7) of the CD38 gene. This alteration results from a A to T substitution at nucleotide position 788, causing the glutamic acid (E) at amino acid position 263 to be replaced by a valine (V). 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	0.28
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.071
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.84	P;.
Vest4		0.24
MutPred		0.67		Loss of disorder (P = 0.0127);.;
MVP		0.45
MPC		0.29
ClinPred		0.86	D
GERP RS		0.55
Varity_R		0.61
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-15842110;