rs12739698

Positions:

• chr1-26903542-G-A

Variant summary

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

The ENST00000435827.6(NUDC):​c.-16+1176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 152,100 control chromosomes in the GnomAD database, including 298 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 0.053 (298 hom., cov: 31)
• Consequence: NUDC ENST00000435827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

Genes affected

NUDC (HGNC:8045): (nuclear distribution C, dynein complex regulator) This gene encodes a nuclear distribution protein that plays an essential role in mitosis and cytokinesis. The encoded protein is involved in spindle formation during mitosis and in microtubule organization during cytokinesis. Pseudogenes of this gene are found on chromosome 2. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDC	XM_024452486.2	c.-16+1176G>A		intron_variant
NUDC	XM_047439143.1	c.-16+1176G>A		intron_variant
NUDC	XM_047439200.1	c.-16+2821G>A		intron_variant
NUDC	XM_047439206.1	c.-16+2462G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDC	ENST00000435827.6	c.-16+1176G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8104 AN: 151982 Hom.: 298 Cov.: 31

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0462

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0508

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

GnomAD4 genome AF: 0.0533 AC: 8106 AN: 152100 Hom.: 298 Cov.: 31 AF XY: 0.0530 AC XY: 3939 AN XY: 74346

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0462

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0445

Gnomad4 FIN AF: 0.0838

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0623 Hom.: 45

Bravo AF: 0.0487

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.7
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12739698; hg19: chr1-27230033;