rs2644700

Positions:

• chr17-879809-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.361-53731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,126 control chromosomes in the GnomAD database, including 1,953 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 0.13 (1953 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: NXN NM_022463.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXN	NM_022463.5	c.361-53731G>A		intron_variant		ENST00000336868.8	NP_071908.2
NXN	XM_005256756.5	c.361-53731G>A		intron_variant			XP_005256813.1
NXN	XM_005256758.4	c.21+17077G>A		intron_variant			XP_005256815.1
NXN	XM_017024949.2	c.361-53731G>A		intron_variant			XP_016880438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXN	ENST00000336868.8	c.361-53731G>A		intron_variant		1	NM_022463.5	ENSP00000337443	P1
	ENST00000573877.1	n.372-71C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20417 AN: 151988 Hom.: 1954 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.100 AC: 2 AN: 20 Hom.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.134 AC: 20434 AN: 152106 Hom.: 1953 Cov.: 32 AF XY: 0.135 AC XY: 10005 AN XY: 74364

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0875

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.0612

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.108

Alfa AF: 0.104 Hom.: 548

Bravo AF: 0.136

Asia WGS AF: 0.163 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.60

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: rs2644700; hg19: chr17-783049;