chr6-46160099-T-A

Variant names:

• chr6-46160099-T-A
• rs2295017
• NM_001290072.2:c.*1227A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290072.2(ENPP5):​c.*1227A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,110 control chromosomes in the GnomAD database, including 7,704 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.

• Frequency:
  • Genomes: 𝑓 0.31 (7704 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENPP5 NM_001290072.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 10 publications found

Genes affected

ENPP5 (HGNC:13717): (ectonucleotide pyrophosphatase/phosphodiesterase family member 5) This gene encodes a type-I transmembrane glycoprotein. Studies in rat suggest the encoded protein may play a role in neuronal cell communications. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP5	NM_001290072.2	c.*1227A>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000371383.7	NP_001277001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP5	ENST00000371383.7	c.*1227A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001290072.2	ENSP00000360436.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46806 AN: 151992 Hom.: 7711 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.349

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.308 AC: 46807 AN: 152110 Hom.: 7704 Cov.: 32 AF XY: 0.308 AC XY: 22917 AN XY: 74360

African (AFR) AF: 0.197 AC: 8167 AN: 41516

American (AMR) AF: 0.332 AC: 5072 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1237 AN: 3460

East Asian (EAS) AF: 0.150 AC: 777 AN: 5182

South Asian (SAS) AF: 0.339 AC: 1634 AN: 4822

European-Finnish (FIN) AF: 0.344 AC: 3634 AN: 10568

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25115 AN: 67962

Other (OTH) AF: 0.348 AC: 736 AN: 2114

Alfa AF: 0.332 Hom.: 1161

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs2295017; hg19: chr6-46127836;