19-5962519-C-T

Position:

• chr19-5962519-C-T

Variant summary

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

The NM_007322.3(RANBP3):​c.23-4546G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,950 control chromosomes in the GnomAD database, including 38,170 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 0.71 (38170 hom., cov: 30)
• Consequence: RANBP3 NM_007322.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32

Genes affected

RANBP3 (HGNC:9850): (RAN binding protein 3) This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP3	NM_007322.3	c.23-4546G>A		intron_variant		ENST00000340578.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP3	ENST00000340578.10	c.23-4546G>A		intron_variant		1	NM_007322.3	P3

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107203 AN: 151832 Hom.: 38134 Cov.: 30

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.706 AC: 107295 AN: 151950 Hom.: 38170 Cov.: 30 AF XY: 0.704 AC XY: 52309 AN XY: 74268

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.701

Alfa AF: 0.691 Hom.: 61227

Bravo AF: 0.725

Asia WGS AF: 0.730 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.062
DANN	Benign	0.49

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: rs639251; hg19: chr19-5962530;