17-79735220-C-G

Variant names:

• chr17-79735220-C-G
• rs80066859
• NM_178543.5:c.577C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_178543.5(ENPP7):​c.577C>G​(p.Leu193Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,452 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L193F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0083 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (13 hom.)
• Consequence: ENPP7 NM_178543.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014483929).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00834 (1271/152330) while in subpopulation AFR AF = 0.0283 (1176/41568). AF 95% confidence interval is 0.0269. There are 15 homozygotes in GnomAd4. There are 599 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

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.577C>G	p.Leu193Val	missense	Exon 3 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.577C>G	p.Leu193Val	missense	Exon 3 of 6	ENSP00000332656.5	Q6UWV6
	ENPP7	ENST00000864480.1		c.577C>G	p.Leu193Val	missense	Exon 4 of 7	ENSP00000534539.1
	ENPP7	ENST00000864481.1		c.577C>G	p.Leu193Val	missense	Exon 3 of 5	ENSP00000534540.1

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 1270 AN: 152212 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00221 AC: 555 AN: 250938 AF XY: 0.00163

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000918 AC: 1342 AN: 1461122 Hom.: 13 Cov.: 33 AF XY: 0.000810 AC XY: 589 AN XY: 726880

African (AFR) AF: 0.0285 AC: 954 AN: 33480

American (AMR) AF: 0.00161 AC: 72 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52676

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.000191 AC: 212 AN: 1111992

Other (OTH) AF: 0.00141 AC: 85 AN: 60388

GnomAD4 genome AF: 0.00834 AC: 1271 AN: 152330 Hom.: 15 Cov.: 32 AF XY: 0.00804 AC XY: 599 AN XY: 74486

African (AFR) AF: 0.0283 AC: 1176 AN: 41568

American (AMR) AF: 0.00385 AC: 59 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68032

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.000682 Hom.: 0

Bravo AF: 0.00903

ESP6500AA AF: 0.0275 AC: 121

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00250 AC: 304

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
MetaRNN	Benign	0.014	T
MetaSVM	Uncertain	-0.0024	T
PhyloP100		2.1
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Vest4		0.54
MVP		0.84
MPC		0.57
ClinPred		0.022	T
GERP RS		4.8
PromoterAI		-0.0032	Neutral
gMVP		0.71
Mutation Taster		=87/13	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: rs80066859; hg19: chr17-77709019;