17-79731200-G-A

Variant names:

• chr17-79731200-G-A
• rs782198567
• NM_178543.5:c.61G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178543.5(ENPP7):​c.61G>A​(p.Gly21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,611,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: ENPP7 NM_178543.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 0 publications found

Genes affected

ENPP7 (HGNC:23764): (ectonucleotide pyrophosphatase/phosphodiesterase 7) The protein encoded by this gene is an intestinal alkaline sphingomyelin phosphodiesterase that converts sphingomyelin to ceramide and phosphocholine. The encoded protein is anchored in the cell membrane, and it may function to protect the intestinal mucosa from inflammation and tumorigenesis. This protein is glycosylated and also exhibits lysophosphatidylcholine hydrolase activity. [provided by RefSeq, Oct 2016]

ENSG00000306583 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10139492).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178543.5. 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
	ENPP7	NM_178543.5	MANE Select	c.61G>A	p.Gly21Arg	missense	Exon 1 of 6	NP_848638.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP7	ENST00000328313.10	TSL:1 MANE Select	c.61G>A	p.Gly21Arg	missense	Exon 1 of 6	ENSP00000332656.5	Q6UWV6
	ENPP7	ENST00000864480.1		c.61G>A	p.Gly21Arg	missense	Exon 2 of 7	ENSP00000534539.1
	ENPP7	ENST00000864481.1		c.61G>A	p.Gly21Arg	missense	Exon 1 of 5	ENSP00000534540.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152184 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000605 AC: 15 AN: 247968 AF XY: 0.0000817

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.0000359

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000466 AC: 68 AN: 1459520 Hom.: 0 Cov.: 62 AF XY: 0.0000455 AC XY: 33 AN XY: 726062

African (AFR) AF: 0.0000299 AC: 1 AN: 33428

American (AMR) AF: 0.0000448 AC: 2 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86112

European-Finnish (FIN) AF: 0.000171 AC: 9 AN: 52646

Middle Eastern (MID) AF: 0.000419 AC: 2 AN: 4772

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111812

Other (OTH) AF: 0.0000664 AC: 4 AN: 60254

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152184 Hom.: 0 Cov.: 34 AF XY: 0.0000942 AC XY: 7 AN XY: 74336

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000470 AC: 5 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.74	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.095
Sift	Uncertain	0.020	D
Sift4G	Benign	0.094	T
Vest4		0.12
MutPred		0.38		Gain of solvent accessibility (P = 0.08)
MVP		0.59
MPC		0.15
ClinPred		0.089	T
GERP RS		2.3
PromoterAI		0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.63
Mutation Taster		=89/11	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: rs782198567; hg19: chr17-77704962;