Genetic Variant SH3RF2:p.Asn161LysfsTer31 (chr5-146000160-AATTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCC-A) – ACMG Classification: Uncertain_significance (2 pts)

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.Asn161LysfsTer31) 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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.59

Variant links:

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]

SH3RF2 links:

LOC107986458 (HGNC:):

LOC107986458 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SH3RF2	NM_152550.4 link	c.483_529delTTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCCA	p.Asn161LysfsTer31	frameshift_variant	Exon 3 of 10	ENST00000359120.9	NP_689763.4	Q8TEC5-1Q08AM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF2	ENST00000359120.9 link	c.483_529delTTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCCA	p.Asn161LysfsTer31	frameshift_variant	Exon 3 of 10	1	NM_152550.4	ENSP00000352028.4		Q8TEC5-1
SH3RF2	ENST00000511217.1 link	c.483_529delTTGGTACCAGGGGGAAATCAATGGCATCAGCGGGAACTTCCCAGCCA	p.Asn161LysfsTer31	frameshift_variant	Exon 2 of 10	1		ENSP00000424497.1		Q8TEC5-1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jun 03, 2024

Clinical Genomics Laboratory, Washington University in St. Louis

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.