14-73977387-GAAAA-G

Position:

• chr14-73977387-GAAAA-G

Variant summary

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

The NM_001249.5(ENTPD5):​c.442-17_442-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,030,300 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: 0)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ENTPD5 NM_001249.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

ENTPD5 (HGNC:3367): (ectonucleoside triphosphate diphosphohydrolase 5 (inactive)) The protein encoded by this gene is similar to E-type nucleotidases (NTPases)/ecto-ATPase/apyrases. NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD5 contains 4 apyrase-conserved regions which is characteristic of NTPases. [provided by RefSeq, Jan 2009]

ACMG classification

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
ENTPD5	NM_001249.5	c.442-17_442-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000334696.11	NP_001240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD5	ENST00000334696.11	c.442-17_442-14del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001249.5	ENSP00000335246	P1
ENTPD5	ENST00000553284.5	c.442-17_442-14del		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000451591
ENTPD5	ENST00000557325.5	c.442-17_442-14del		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000451810

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000214 AC: 22 AN: 1030300 Hom.: 0 AF XY: 0.0000171 AC XY: 9 AN XY: 526466

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000324

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000287

Gnomad4 SAS exome AF: 0.0000145

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.0000196

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs201751093; hg19: chr14-74444090;