rs2360111

chr17-928427-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022463.5(NXN):c.360+50892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,050 control chromosomes in the GnomAD database, including 9,869 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9869 hom., cov: 32)
• Consequence: NXN NM_022463.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXN	NM_022463.5	c.360+50892G>A		intron_variant		ENST00000336868.8
NXN	XM_005256756.5	c.360+50892G>A		intron_variant
NXN	XM_017024949.2	c.360+50892G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXN	ENST00000336868.8	c.360+50892G>A		intron_variant		1	NM_022463.5	P1
NXN	ENST00000571338.1	n.389+1236G>A		intron_variant, non_coding_transcript_variant		4
NXN	ENST00000575171.1	n.31+50892G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52779 AN: 151930 Hom.: 9868 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52809 AN: 152050 Hom.: 9869 Cov.: 32 AF XY: 0.346 AC XY: 25705 AN XY: 74300

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.370

Alfa AF: 0.397 Hom.: 25649

Bravo AF: 0.346

Asia WGS AF: 0.386 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.5
Dann	Benign	0.62

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: rs2360111; hg19: chr17-831667;