rs193920826

Variant names:

• chr17-79731207-C-A
• rs193920826
• NM_178543.5:c.68C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-79731207-C-A
• chr17-79731207-C-T

Variant summary

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

The NM_178543.5(ENPP7):​c.68C>A​(p.Pro23Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P23L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ENPP7 NM_178543.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP7	NM_178543.5	c.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 6	ENST00000328313.10	NP_848638.3
ENPP7	XM_011524737.2	c.161C>A	p.Pro54Gln	missense_variant	Exon 1 of 5		XP_011523039.2
ENPP7	XR_001752505.2	n.265C>A		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP7	ENST00000328313.10	c.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 6	1	NM_178543.5	ENSP00000332656.5
ENSG00000306583	ENST00000819500.1	n.208+1354G>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459884 Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0 AN XY: 726258

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4894

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111878

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.92
Eigen	Benign	0.16
Eigen_PC	Benign	0.099
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.58	T
PhyloP100		3.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.013	D
Vest4		0.61
MutPred		0.30		Gain of sheet (P = 0.0028);
MVP		0.70
MPC		0.11
ClinPred		0.72	D
GERP RS		4.6
PromoterAI		0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.71
Mutation Taster		=73/27	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: rs193920826; hg19: chr17-77704969;