6-85467248-C-T

Variant names:

• chr6-85467248-C-T
• rs74858361
• NM_002526.4:c.528C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_002526.4(NT5E):​c.528C>T​(p.Tyr176Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,146 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (53 hom.)
• Consequence: NT5E NM_002526.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158
• Publications: 4 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 (BayesDel_noAF=-0.46).
• BP6: Variant 6-85467248-C-T is Benign according to our data. Variant chr6-85467248-C-T is described in ClinVar as Benign. ClinVar VariationId is 717329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.158 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00153 (233/152304) while in subpopulation EAS AF = 0.0417 (216/5176). AF 95% confidence interval is 0.0372. There are 3 homozygotes in GnomAd4. There are 137 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.528C>T	p.Tyr176Tyr	synonymous	Exon 2 of 9	NP_002517.1	P21589-1
	NT5E	NM_001204813.2		c.528C>T	p.Tyr176Tyr	synonymous	Exon 2 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.528C>T	p.Tyr176Tyr	synonymous	Exon 2 of 9	ENSP00000257770.3	P21589-1
	NT5E	ENST00000369646.7	TSL:1	c.528C>T	p.Tyr176Tyr	synonymous	Exon 2 of 3	ENSP00000358660.3	Q96B60
	NT5E	ENST00000880507.1		c.528C>T	p.Tyr176Tyr	synonymous	Exon 2 of 10	ENSP00000550566.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152186 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00418 AC: 1050 AN: 251204 AF XY: 0.00386

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0552

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00141 AC: 2064 AN: 1461842 Hom.: 53 Cov.: 32 AF XY: 0.00136 AC XY: 990 AN XY: 727224

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0470 AC: 1866 AN: 39690

South Asian (SAS) AF: 0.000475 AC: 41 AN: 86258

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

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1111980

Other (OTH) AF: 0.00166 AC: 100 AN: 60392

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152304 Hom.: 3 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74468

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.000457 AC: 7 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5176

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000234 Hom.: 0

Bravo AF: 0.00204

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	-0.46
CADD	Benign	3.1
DANN	Benign	0.44
PhyloP100		-0.16
Mutation Taster		=100/0	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: rs74858361; hg19: chr6-86176966;