14-73977387-GAAAAAA-GAAAAA

Variant names:

• chr14-73977387-GA-G
• rs201751093
• NM_001249.5:c.442-14delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000334696.11(ENTPD5):​c.442-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (40 hom., cov: 0)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: ENTPD5 ENST00000334696.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0147 (1800/122206) while in subpopulation AFR AF = 0.0514 (1597/31048). AF 95% confidence interval is 0.0493. There are 40 homozygotes in GnomAd4. There are 824 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334696.11. 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.442-14delT		intron	N/A	NP_001240.1
	ENTPD5	NM_001321985.3		c.442-14delT		intron	N/A	NP_001308914.1
	ENTPD5	NM_001321986.3		c.442-14delT		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.442-14delT		intron	N/A	ENSP00000335246.6
	ENTPD5	ENST00000557325.5	TSL:2	c.442-14delT		intron	N/A	ENSP00000451810.1
	ENTPD5	ENST00000553284.5	TSL:3	c.442-14delT		intron	N/A	ENSP00000451591.1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 1791 AN: 122186 Hom.: 39 Cov.: 0

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00664

Gnomad ASJ AF: 0.000974

Gnomad EAS AF: 0.00112

Gnomad SAS AF: 0.000547

Gnomad FIN AF: 0.00333

Gnomad MID AF: 0.0115

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0133

GnomAD2 exomes AF: 0.192 AC: 27472 AN: 143370 AF XY: 0.191

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.368

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.119 AC: 117097 AN: 981186 Hom.: 3 Cov.: 14 AF XY: 0.121 AC XY: 60633 AN XY: 499134

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

African (AFR) AF: 0.236 AC: 4983 AN: 21144

American (AMR) AF: 0.166 AC: 4790 AN: 28784

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 2529 AN: 19850

East Asian (EAS) AF: 0.286 AC: 8693 AN: 30374

South Asian (SAS) AF: 0.178 AC: 11041 AN: 61864

European-Finnish (FIN) AF: 0.108 AC: 4048 AN: 37592

Middle Eastern (MID) AF: 0.123 AC: 516 AN: 4188

European-Non Finnish (NFE) AF: 0.102 AC: 74959 AN: 735118

Other (OTH) AF: 0.131 AC: 5538 AN: 42272

⚠️ 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 AF: 0.0147 AC: 1800 AN: 122206 Hom.: 40 Cov.: 0 AF XY: 0.0141 AC XY: 824 AN XY: 58470

African (AFR) AF: 0.0514 AC: 1597 AN: 31048

American (AMR) AF: 0.00663 AC: 81 AN: 12218

Ashkenazi Jewish (ASJ) AF: 0.000974 AC: 3 AN: 3080

East Asian (EAS) AF: 0.00141 AC: 5 AN: 3550

South Asian (SAS) AF: 0.000550 AC: 2 AN: 3634

European-Finnish (FIN) AF: 0.00333 AC: 22 AN: 6600

Middle Eastern (MID) AF: 0.0125 AC: 3 AN: 240

European-Non Finnish (NFE) AF: 0.00109 AC: 65 AN: 59390

Other (OTH) AF: 0.0133 AC: 22 AN: 1660

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201751093; hg19: chr14-74444090; COSMIC: COSV58220492; COSMIC: COSV58220492;