rs143316789

Variant names:

• chrX-130631526-A-G
• rs143316789
• NM_006375.4:c.1470T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006375.4(ENOX2):​c.1470T>C​(p.Pro490Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,204,822 control chromosomes in the GnomAD database, including 3 homozygotes. There are 922 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., 65 hem., cov: 22)
  • Exomes 𝑓: 0.0025 (3 hom. 857 hem.)
• Consequence: ENOX2 NM_006375.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.171
• Publications: 0 publications found

Genes affected

ENOX2 (HGNC:2259): (ecto-NOX disulfide-thiol exchanger 2) This gene is a tumor-specific member of the ECTO-NOX family of genes that encode cell surface NADH oxidases. The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The protein also displays prion-like properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant X-130631526-A-G is Benign according to our data. Variant chrX-130631526-A-G is described in ClinVar as Benign. ClinVar VariationId is 719414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.171 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 65 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006375.4. 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
	ENOX2	NM_006375.4	MANE Select	c.1470T>C	p.Pro490Pro	synonymous	Exon 13 of 15	NP_006366.2
	ENOX2	NM_001382518.1		c.1746T>C	p.Pro582Pro	synonymous	Exon 14 of 16	NP_001369447.1	A0A8I5KRI1
	ENOX2	NM_001382516.1		c.1557T>C	p.Pro519Pro	synonymous	Exon 16 of 18	NP_001369445.1	Q16206-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX2	ENST00000394363.6	TSL:2 MANE Select	c.1470T>C	p.Pro490Pro	synonymous	Exon 13 of 15	ENSP00000377890.1	Q16206-2
	ENOX2	ENST00000370927.5	TSL:1	c.1557T>C	p.Pro519Pro	synonymous	Exon 11 of 13	ENSP00000359965.1	Q16206-1
	ENOX2	ENST00000686943.1		c.1746T>C	p.Pro582Pro	synonymous	Exon 14 of 16	ENSP00000509235.1	A0A8I5KRI1

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 224 AN: 111750 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000761

Gnomad ASJ AF: 0.000378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00629

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00305

Gnomad OTH AF: 0.00398

GnomAD2 exomes AF: 0.00200 AC: 366 AN: 183282 AF XY: 0.00189

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.000438

Gnomad ASJ exome AF: 0.000802

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00684

Gnomad NFE exome AF: 0.00271

Gnomad OTH exome AF: 0.00177

GnomAD4 exome AF: 0.00252 AC: 2749 AN: 1093019 Hom.: 3 Cov.: 27 AF XY: 0.00239 AC XY: 857 AN XY: 358595

African (AFR) AF: 0.000190 AC: 5 AN: 26302

American (AMR) AF: 0.000426 AC: 15 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.000258 AC: 5 AN: 19349

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.000407 AC: 22 AN: 54017

European-Finnish (FIN) AF: 0.00817 AC: 331 AN: 40504

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4125

European-Non Finnish (NFE) AF: 0.00272 AC: 2276 AN: 837416

Other (OTH) AF: 0.00205 AC: 94 AN: 45917

GnomAD4 genome AF: 0.00200 AC: 224 AN: 111803 Hom.: 0 Cov.: 22 AF XY: 0.00191 AC XY: 65 AN XY: 33973

African (AFR) AF: 0.000292 AC: 9 AN: 30805

American (AMR) AF: 0.000761 AC: 8 AN: 10519

Ashkenazi Jewish (ASJ) AF: 0.000378 AC: 1 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3549

South Asian (SAS) AF: 0.00 AC: 0 AN: 2651

European-Finnish (FIN) AF: 0.00629 AC: 38 AN: 6043

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00305 AC: 162 AN: 53155

Other (OTH) AF: 0.00393 AC: 6 AN: 1528

Alfa AF: 0.00196 Hom.: 16

Bravo AF: 0.00161

EpiCase AF: 0.00219

EpiControl AF: 0.00219

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	-0.59
CADD	Benign	9.7
DANN	Benign	0.70
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143316789; hg19: chrX-129765500;