14-73974979-C-G

Variant names:

• chr14-73974979-C-G
• NM_001249.5:c.729G>C
• ENTPD5 p.Leu243Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001249.5(ENTPD5):​c.729G>C​(p.Leu243Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTPD5 NM_001249.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=1.76 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD5	NM_001249.5	MANE Select	c.729G>C	p.Leu243Leu	synonymous	Exon 11 of 16	NP_001240.1	O75356
	ENTPD5	NM_001321985.3		c.729G>C	p.Leu243Leu	synonymous	Exon 12 of 17	NP_001308914.1	O75356
	ENTPD5	NM_001321986.3		c.729G>C	p.Leu243Leu	synonymous	Exon 12 of 17	NP_001308915.1	O75356

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD5	ENST00000334696.11	TSL:5 MANE Select	c.729G>C	p.Leu243Leu	synonymous	Exon 11 of 16	ENSP00000335246.6	O75356
	ENTPD5	ENST00000900912.1		c.753G>C	p.Leu251Leu	synonymous	Exon 9 of 14	ENSP00000570971.1
	ENTPD5	ENST00000900901.1		c.738G>C	p.Leu246Leu	synonymous	Exon 10 of 15	ENSP00000570960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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

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

Other links and lift over

hg19: chr14-74441682;