rs35478984

Variant names:

• chr6-85485380-C-T
• rs35478984
• NM_002526.4:c.897C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-85485380-C-T
• chr6-85485380-C-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_002526.4(NT5E):​c.897C>T​(p.Asn299Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,614,140 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (93 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (74 hom.)
• Consequence: NT5E NM_002526.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710
• Publications: 0 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, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.152).
• BP6: Variant 6-85485380-C-T is Benign according to our data. Variant chr6-85485380-C-T is described in ClinVar as Benign. ClinVar VariationId is 774184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.071 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002526.4. 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
	NT5E	NM_002526.4	MANE Select	c.897C>T	p.Asn299Asn	synonymous	Exon 4 of 9	NP_002517.1	P21589-1
	NT5E	NM_001204813.2		c.897C>T	p.Asn299Asn	synonymous	Exon 4 of 8	NP_001191742.1	P21589-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5E	ENST00000257770.8	TSL:1 MANE Select	c.897C>T	p.Asn299Asn	synonymous	Exon 4 of 9	ENSP00000257770.3	P21589-1
	NT5E	ENST00000880507.1		c.897C>T	p.Asn299Asn	synonymous	Exon 4 of 10	ENSP00000550566.1
	NT5E	ENST00000880506.1		c.897C>T	p.Asn299Asn	synonymous	Exon 4 of 9	ENSP00000550565.1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2845 AN: 152168 Hom.: 91 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00488 AC: 1227 AN: 251312 AF XY: 0.00324

Gnomad AFR exome AF: 0.0639

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00181 AC: 2642 AN: 1461854 Hom.: 74 Cov.: 32 AF XY: 0.00151 AC XY: 1099 AN XY: 727236

African (AFR) AF: 0.0601 AC: 2013 AN: 33470

American (AMR) AF: 0.00376 AC: 168 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 46 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00537 AC: 31 AN: 5768

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1111994

Other (OTH) AF: 0.00412 AC: 249 AN: 60392

GnomAD4 genome AF: 0.0188 AC: 2868 AN: 152286 Hom.: 93 Cov.: 33 AF XY: 0.0184 AC XY: 1370 AN XY: 74446

African (AFR) AF: 0.0649 AC: 2696 AN: 41556

American (AMR) AF: 0.00752 AC: 115 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68026

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.00668 Hom.: 11

Bravo AF: 0.0203

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	5.3
DANN	Benign	0.60
PhyloP100		-0.071
PromoterAI		-0.078	Neutral
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: rs35478984; hg19: chr6-86195098;