rs9444348

Variant names:

• chr6-85465856-G-A
• rs9444348
• NM_002526.4:c.340-1204G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-85465856-G-A
• chr6-85465856-G-T

Variant summary

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

The NM_002526.4(NT5E):​c.340-1204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,064 control chromosomes in the GnomAD database, including 15,732 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 0.43 (15732 hom., cov: 32)
• Consequence: NT5E NM_002526.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 17 publications found

Genes affected

NT5E (HGNC:8021): (5'-nucleotidase ecto) The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

NT5E Gene-Disease associations (from GenCC):

• hereditary arterial and articular multiple calcification syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5E	NM_002526.4	c.340-1204G>A		intron_variant	Intron 1 of 8	ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.340-1204G>A		intron_variant	Intron 1 of 7		NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.340-1204G>A		intron_variant	Intron 1 of 8	1	NM_002526.4	ENSP00000257770.3
NT5E	ENST00000369646.7	c.340-1204G>A		intron_variant	Intron 1 of 2	1		ENSP00000358660.3
NT5E	ENST00000369651.7	c.340-1204G>A		intron_variant	Intron 1 of 7	2		ENSP00000358665.3

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66021 AN: 151942 Hom.: 15719 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 66081 AN: 152064 Hom.: 15732 Cov.: 32 AF XY: 0.438 AC XY: 32549 AN XY: 74334

African (AFR) AF: 0.234 AC: 9698 AN: 41514

American (AMR) AF: 0.572 AC: 8731 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1934 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5164

South Asian (SAS) AF: 0.495 AC: 2382 AN: 4814

European-Finnish (FIN) AF: 0.501 AC: 5298 AN: 10572

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34685 AN: 67964

Other (OTH) AF: 0.467 AC: 982 AN: 2102

Alfa AF: 0.485 Hom.: 9153

Bravo AF: 0.435

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.9
DANN	Benign	0.87
PhyloP100		-0.88
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: rs9444348; hg19: chr6-86175574;