chr3-40392091-C-T

Position:

• chr3-40392091-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001248.4(ENTPD3):​c.109C>T​(p.Leu37Phe) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTPD3 NM_001248.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.445

Genes affected

ENTPD3 (HGNC:3365): (ectonucleoside triphosphate diphosphohydrolase 3) This gene encodes a plasma membrane-bound divalent cation-dependent E-type nucleotidase. The encoded protein is involved in the regulation of extracellular levels of ATP by hydrolysis of it and other nucleotides. Multiple transcript variants have been described. [provided by RefSeq, May 2014]

ENTPD3-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23351246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD3	NM_001248.4	c.109C>T	p.Leu37Phe	missense_variant	3/11	ENST00000301825.8	NP_001239.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD3	ENST00000301825.8	c.109C>T	p.Leu37Phe	missense_variant	3/11	1	NM_001248.4	ENSP00000301825.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

The c.109C>T (p.L37F) alteration is located in exon 3 (coding exon 2) of the ENTPD3 gene. This alteration results from a C to T substitution at nucleotide position 109, causing the leucine (L) at amino acid position 37 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.77	.;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;L;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.6	D;N;D;N
REVEL	Benign	0.099
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.35
MutPred		0.29		Gain of catalytic residue at L37 (P = 0.0902);Gain of catalytic residue at L37 (P = 0.0902);Gain of catalytic residue at L37 (P = 0.0902);Gain of catalytic residue at L37 (P = 0.0902);
MVP		0.61
MPC		0.32
ClinPred		0.90	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-40433582;