5-145959998-C-T

Variant names:

• chr5-145959998-C-T
• rs4913054
• NM_152550.4:c.378+21692C>T

Variant summary

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

The NM_152550.4(SH3RF2):​c.378+21692C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 152,112 control chromosomes in the GnomAD database, including 1,048 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 0.096 (1048 hom., cov: 32)
• Consequence: SH3RF2 NM_152550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF2	NM_152550.4	c.378+21692C>T		intron_variant	Intron 2 of 9	ENST00000359120.9	NP_689763.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF2	ENST00000359120.9	c.378+21692C>T		intron_variant	Intron 2 of 9	1	NM_152550.4	ENSP00000352028.4
SH3RF2	ENST00000511217.1	c.378+21692C>T		intron_variant	Intron 1 of 9	1		ENSP00000424497.1

Frequencies

GnomAD3 genomes AF: 0.0960 AC: 14595 AN: 151994 Hom.: 1048 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0959 AC: 14594 AN: 152112 Hom.: 1048 Cov.: 32 AF XY: 0.101 AC XY: 7529 AN XY: 74348

African (AFR) AF: 0.0222 AC: 921 AN: 41496

American (AMR) AF: 0.181 AC: 2764 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 262 AN: 3464

East Asian (EAS) AF: 0.267 AC: 1374 AN: 5150

South Asian (SAS) AF: 0.203 AC: 976 AN: 4816

European-Finnish (FIN) AF: 0.121 AC: 1277 AN: 10572

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6780 AN: 67998

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.0944 Hom.: 105

Bravo AF: 0.0944

Asia WGS AF: 0.206 AC: 715 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	0.96
DANN	Benign	0.67
PhyloP100		-0.20
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: rs4913054; hg19: chr5-145339561;