rs1599386

Positions:

• chr3-161138526-A-G
• chr3-161138526-A-T

Variant summary

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

The ENST00000460503.5(NMD3):​c.-21+33645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,984 control chromosomes in the GnomAD database, including 34,719 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 0.65 (34719 hom., cov: 31)
• Consequence: NMD3 ENST00000460503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

Genes affected

NMD3 (HGNC:24250): (NMD3 ribosome export adaptor) Ribosomal 40S and 60S subunits associate in the nucleolus and are exported to the cytoplasm. The protein encoded by this gene is involved in the passage of the 60S subunit through the nuclear pore complex and into the cytoplasm. Several transcript variants exist for this gene, but the full-length natures of only two have been described to date. [provided by RefSeq, Feb 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.161138526A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMD3	ENST00000460503.5	c.-21+33645A>G		intron_variant		4		ENSP00000418980.1
NMD3	ENST00000468606.5	c.-105-18445A>G		intron_variant		5		ENSP00000418852.1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99285 AN: 151866 Hom.: 34659 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.654 AC: 99407 AN: 151984 Hom.: 34719 Cov.: 31 AF XY: 0.656 AC XY: 48712 AN XY: 74244

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.618

Alfa AF: 0.603 Hom.: 4937

Bravo AF: 0.677

Asia WGS AF: 0.868 AC: 3017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1599386; hg19: chr3-160856314;