4-15848540-CCT-ACC

Variant names:

• chr4-15848540-CCT-ACC
• NM_001775.4:c.841_843delCCTinsACC
• CD38 p.Pro281Thr

Variant summary

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

The NM_001775.4(CD38):​c.841_843delCCTinsACC​(p.Pro281Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P281S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD38 NM_001775.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 0 publications found

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]

ENSG00000304423 (HGNC:58740):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	NM_001775.4	MANE Select	c.841_843delCCTinsACC	p.Pro281Thr	missense splice_region	N/A	NP_001766.2
	CD38	NR_132660.2		n.792_794delCCTinsACC		splice_region non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.841_843delCCTinsACC	p.Pro281Thr	missense splice_region	N/A	ENSP00000226279.2	P28907-1
	CD38	ENST00000502843.5	TSL:1	n.*336_*338delCCTinsACC		splice_region non_coding_transcript_exon	Exon 7 of 7	ENSP00000427277.1	P28907-2
	CD38	ENST00000502843.5	TSL:1	n.*336_*338delCCTinsACC		3_prime_UTR	Exon 7 of 7	ENSP00000427277.1	P28907-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-15850163;