rs604229

Positions:

• chr17-883588-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.361-57510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,272 control chromosomes in the GnomAD database, including 1,300 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 0.12 (1300 hom., cov: 33)
• Consequence: NXN NM_022463.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXN	NM_022463.5	c.361-57510G>A		intron_variant		ENST00000336868.8
NXN	XM_005256756.5	c.361-57510G>A		intron_variant
NXN	XM_005256758.4	c.21+13298G>A		intron_variant
NXN	XM_017024949.2	c.361-57510G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXN	ENST00000336868.8	c.361-57510G>A		intron_variant		1	NM_022463.5	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18508 AN: 152154 Hom.: 1302 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.121 AC: 18496 AN: 152272 Hom.: 1300 Cov.: 33 AF XY: 0.127 AC XY: 9426 AN XY: 74456

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0927

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0871 Hom.: 1023

Bravo AF: 0.127

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.70

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: rs604229; hg19: chr17-786828;