chr5-146000160-AATTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCC-A

Position:

• chr5-146000160-AATTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCC-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152550.4(SH3RF2):​c.483_529delTTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCCA​(p.Asn161fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH3RF2 NM_152550.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.59

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3RF2	NM_152550.4	c.483_529delTTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCCA	p.Asn161fs	frameshift_variant	3/10	ENST00000359120.9	NP_689763.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3RF2	ENST00000359120.9	c.483_529delTTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCCA	p.Asn161fs	frameshift_variant	3/10	1	NM_152550.4	ENSP00000352028.4
SH3RF2	ENST00000511217.1	c.483_529delTTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCCA	p.Asn161fs	frameshift_variant	2/10	1		ENSP00000424497.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genomics Laboratory, Washington University in St. Louis

Jun 03, 2024

The SH3RF2 c.483_529del ( p.Asn161Lysfs*31) variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by deleting 47 nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Due to limited information, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-145379723;