6-85450181-C-G

Variant names:

• chr6-85450181-C-G
• rs368613430
• NM_002526.4:c.42C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002526.4(NT5E):​c.42C>G​(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L14L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5E NM_002526.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-0.552 with no splicing effect.

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.42C>G	p.Leu14Leu	synonymous	Exon 1 of 9	NP_002517.1	P21589-1
	NT5E	NM_001204813.2		c.42C>G	p.Leu14Leu	synonymous	Exon 1 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.42C>G	p.Leu14Leu	synonymous	Exon 1 of 9	ENSP00000257770.3	P21589-1
	NT5E	ENST00000369646.7	TSL:1	c.42C>G	p.Leu14Leu	synonymous	Exon 1 of 3	ENSP00000358660.3	Q96B60
	NT5E	ENST00000880507.1		c.42C>G	p.Leu14Leu	synonymous	Exon 1 of 10	ENSP00000550566.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.35
DANN	Benign	0.37
PhyloP100		-0.55
PromoterAI		0.026	Neutral

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: rs368613430; hg19: chr6-86159899;