chr14-73977387-GAAAAAA-G

Variant names:

• chr14-73977387-GAAAAAA-G
• rs201751093
• NM_001249.5:c.442-19_442-14delTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001249.5(ENTPD5):​c.442-19_442-14delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000097 in 1,030,624 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: 9.7e-7 (0 hom.)
• Consequence: ENTPD5 NM_001249.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001249.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD5	NM_001249.5	MANE Select	c.442-19_442-14delTTTTTT		intron	N/A	NP_001240.1
	ENTPD5	NM_001321985.3		c.442-19_442-14delTTTTTT		intron	N/A	NP_001308914.1
	ENTPD5	NM_001321986.3		c.442-19_442-14delTTTTTT		intron	N/A	NP_001308915.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD5	ENST00000334696.11	TSL:5 MANE Select	c.442-19_442-14delTTTTTT		intron	N/A	ENSP00000335246.6
	ENTPD5	ENST00000900912.1		c.466-19_466-14delTTTTTT		intron	N/A	ENSP00000570971.1
	ENTPD5	ENST00000900901.1		c.442-19_442-14delTTTTTT		intron	N/A	ENSP00000570960.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 9.70e-7 AC: 1 AN: 1030624 Hom.: 0 AF XY: 0.00000190 AC XY: 1 AN XY: 526640

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22748

American (AMR) AF: 0.00 AC: 0 AN: 30854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21024

East Asian (EAS) AF: 0.00 AC: 0 AN: 34824

South Asian (SAS) AF: 0.00 AC: 0 AN: 68828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4452

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 763638

Other (OTH) AF: 0.00 AC: 0 AN: 44624

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

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

Other links and lift over

dbSNP: rs201751093; hg19: chr14-74444090;