17-801240-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022463.5(NXN):c.1126-109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 782,936 control chromosomes in the GnomAD database, including 150,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (32746 hom., cov: 30)
  • Exomes 𝑓: 0.61 (117684 hom.)
• Consequence: NXN NM_022463.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.516

Genes affected

NXN (HGNC:18008): (nucleoredoxin) This gene encodes a member of the thioredoxin superfamily, a group of small, multifunctional redox-active proteins. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. The encoded protein acts a redox-dependent regulator of the Wnt signaling pathway and is involved in cell growth and differentiation. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-801240-C-A is Benign according to our data. Variant chr17-801240-C-A is described in ClinVar as [Benign]. Clinvar id is 1266203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXN	NM_022463.5	c.1126-109G>T		intron_variant		ENST00000336868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXN	ENST00000336868.8	c.1126-109G>T		intron_variant		1	NM_022463.5	P1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 98935 AN: 151576 Hom.: 32692 Cov.: 30

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.606 AC: 382660 AN: 631240 Hom.: 117684 AF XY: 0.607 AC XY: 187968 AN XY: 309886

Gnomad4 AFR exome AF: 0.705

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.641

Gnomad4 EAS exome AF: 0.768

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.709

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.621

GnomAD4 genome AF: 0.653 AC: 99054 AN: 151696 Hom.: 32746 Cov.: 30 AF XY: 0.662 AC XY: 49038 AN XY: 74120

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.641

Alfa AF: 0.618 Hom.: 3458

Bravo AF: 0.655

Asia WGS AF: 0.727 AC: 2528 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.84
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs570710; hg19: chr17-704480; COSMIC: COSV61095090;