17-79735220-C-T

Variant names:

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

Variant summary

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

The NM_178543.5(ENPP7):​c.577C>T​(p.Leu193Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENPP7 NM_178543.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Leu193Phe	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>T	p.Leu193Phe	missense	Exon 3 of 6	ENSP00000332656.5	Q6UWV6
	ENPP7	ENST00000864480.1		c.577C>T	p.Leu193Phe	missense	Exon 4 of 7	ENSP00000534539.1
	ENPP7	ENST00000864481.1		c.577C>T	p.Leu193Phe	missense	Exon 3 of 5	ENSP00000534540.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.38	D
PhyloP100		2.1
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.64
Sift	Benign	0.067	T
Sift4G	Pathogenic	0.0	D
Vest4		0.31
MutPred		0.64		Loss of stability (P = 0.0879)
MVP		0.85
MPC		0.52
ClinPred		0.95	D
GERP RS		4.8
PromoterAI		0.0036	Neutral
gMVP		0.80

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;