rs9325002

Variant names:

• chr5-146046685-T-C
• rs9325002
• NM_152550.4:c.1060-1087T>C

Variant summary

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

The NM_152550.4(SH3RF2):​c.1060-1087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,098 control chromosomes in the GnomAD database, including 7,700 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 0.28 (7700 hom., cov: 32)
• Consequence: SH3RF2 NM_152550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 1 publications found

Genes affected

SH3RF2 (HGNC:26299): (SH3 domain containing ring finger 2) Enables protein phosphatase 1 binding activity and ubiquitin protein ligase activity. Involved in several processes, including positive regulation of JNK cascade; protein autoubiquitination; and regulation of cellular protein metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC107986458 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF2	NM_152550.4	c.1060-1087T>C		intron_variant	Intron 5 of 9	ENST00000359120.9	NP_689763.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF2	ENST00000359120.9	c.1060-1087T>C		intron_variant	Intron 5 of 9	1	NM_152550.4	ENSP00000352028.4
SH3RF2	ENST00000511217.1	c.1060-1087T>C		intron_variant	Intron 4 of 9	1		ENSP00000424497.1
SH3RF2	ENST00000509286.1	n.187-1087T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42975 AN: 151982 Hom.: 7692 Cov.: 32

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.283 AC: 42995 AN: 152098 Hom.: 7700 Cov.: 32 AF XY: 0.281 AC XY: 20914 AN XY: 74352

African (AFR) AF: 0.0679 AC: 2821 AN: 41530

American (AMR) AF: 0.334 AC: 5098 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3466

East Asian (EAS) AF: 0.292 AC: 1512 AN: 5170

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4818

European-Finnish (FIN) AF: 0.422 AC: 4456 AN: 10550

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26140 AN: 67966

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.329 Hom.: 1261

Bravo AF: 0.271

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs9325002; hg19: chr5-145426248;