14-73977387-GAA-G

Variant names:

• chr14-73977387-GAA-G
• rs201751093
• NM_001249.5:c.442-15_442-14delTT

Variant summary

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

The ENST00000334696.11(ENTPD5):​c.442-15_442-14delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,137,072 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: 𝑓 0.0016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0044 (0 hom.)
• Consequence: ENTPD5 ENST00000334696.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• 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: Variant has high frequency in the AFR (0.0128) population. However there is too low homozygotes in high coverage region: (expected more than 4, got 0).

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.442-15_442-14delTT		intron	N/A	NP_001240.1
	ENTPD5	NM_001321985.3		c.442-15_442-14delTT		intron	N/A	NP_001308914.1
	ENTPD5	NM_001321986.3		c.442-15_442-14delTT		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.442-15_442-14delTT		intron	N/A	ENSP00000335246.6
	ENTPD5	ENST00000557325.5	TSL:2	c.442-15_442-14delTT		intron	N/A	ENSP00000451810.1
	ENTPD5	ENST00000553284.5	TSL:3	c.442-15_442-14delTT		intron	N/A	ENSP00000451591.1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 193 AN: 122278 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00596

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000336

Gnomad OTH AF: 0.000606

GnomAD2 exomes AF: 0.00995 AC: 1426 AN: 143370 AF XY: 0.00980

Gnomad AFR exome AF: 0.0264

Gnomad AMR exome AF: 0.00852

Gnomad ASJ exome AF: 0.00523

Gnomad EAS exome AF: 0.0145

Gnomad FIN exome AF: 0.00770

Gnomad NFE exome AF: 0.00839

Gnomad OTH exome AF: 0.00930

GnomAD4 exome AF: 0.00441 AC: 4480 AN: 1014772 Hom.: 0 AF XY: 0.00431 AC XY: 2236 AN XY: 518390

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

African (AFR) AF: 0.0141 AC: 312 AN: 22134

American (AMR) AF: 0.00786 AC: 237 AN: 30150

Ashkenazi Jewish (ASJ) AF: 0.00431 AC: 89 AN: 20668

East Asian (EAS) AF: 0.00858 AC: 286 AN: 33316

South Asian (SAS) AF: 0.00413 AC: 278 AN: 67298

European-Finnish (FIN) AF: 0.00487 AC: 190 AN: 39018

Middle Eastern (MID) AF: 0.00364 AC: 16 AN: 4392

European-Non Finnish (NFE) AF: 0.00381 AC: 2875 AN: 753888

Other (OTH) AF: 0.00449 AC: 197 AN: 43908

⚠️ 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: 0.00158 AC: 193 AN: 122300 Hom.: 0 Cov.: 0 AF XY: 0.00159 AC XY: 93 AN XY: 58540

African (AFR) AF: 0.00595 AC: 185 AN: 31070

American (AMR) AF: 0.000327 AC: 4 AN: 12226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3086

East Asian (EAS) AF: 0.00 AC: 0 AN: 3552

South Asian (SAS) AF: 0.00 AC: 0 AN: 3636

European-Finnish (FIN) AF: 0.000151 AC: 1 AN: 6606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000336 AC: 2 AN: 59438

Other (OTH) AF: 0.000602 AC: 1 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		-0.12
Mutation Taster		=98/2	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;