rs6707697

Variant names:

• chr2-109323868-T-G
• rs6707697
• NM_001099289.3:c.574-23806T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099289.3(SH3RF3):​c.574-23806T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,334 control chromosomes in the GnomAD database, including 135 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 0.040 (135 hom., cov: 33)
• Consequence: SH3RF3 NM_001099289.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 2 publications found

Genes affected

SH3RF3 (HGNC:24699): (SH3 domain containing ring finger 3) Enables ubiquitin protein ligase activity. Involved in positive regulation of JNK cascade and protein autoubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

RANBP2 Gene-Disease associations (from GenCC):

• familial acute necrotizing encephalopathy

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF3	NM_001099289.3	c.574-23806T>G		intron_variant	Intron 1 of 9	ENST00000309415.8	NP_001092759.1
RANBP2	XM_047445367.1	c.8371-517536T>G		intron_variant	Intron 24 of 24		XP_047301323.1
SH3RF3	XM_011511109.3	c.574-23806T>G		intron_variant	Intron 1 of 8		XP_011509411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF3	ENST00000309415.8	c.574-23806T>G		intron_variant	Intron 1 of 9	5	NM_001099289.3	ENSP00000309186.6

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6026 AN: 152216 Hom.: 135 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0393

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

GnomAD4 genome AF: 0.0395 AC: 6021 AN: 152334 Hom.: 135 Cov.: 33 AF XY: 0.0377 AC XY: 2808 AN XY: 74498

African (AFR) AF: 0.0114 AC: 474 AN: 41580

American (AMR) AF: 0.0449 AC: 687 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.0192 AC: 93 AN: 4834

European-Finnish (FIN) AF: 0.0306 AC: 325 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0614 AC: 4178 AN: 68024

Other (OTH) AF: 0.0389 AC: 82 AN: 2110

Alfa AF: 0.0563 Hom.: 236

Bravo AF: 0.0392

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.60
DANN	Benign	0.76
PhyloP100		-0.18

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

Other links and lift over

dbSNP: rs6707697; hg19: chr2-109940324;