rs200055659

Variant names:

• chr5-145938070-C-G
• NM_152550.4:c.142C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-145938070-C-G
• chr5-145938070-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152550.4(SH3RF2):​c.142C>G​(p.Arg48Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R48W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SH3RF2 NM_152550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF2	NM_152550.4	c.142C>G	p.Arg48Gly	missense_variant	Exon 2 of 10	ENST00000359120.9	NP_689763.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF2	ENST00000359120.9	c.142C>G	p.Arg48Gly	missense_variant	Exon 2 of 10	1	NM_152550.4	ENSP00000352028.4
SH3RF2	ENST00000511217.1	c.142C>G	p.Arg48Gly	missense_variant	Exon 1 of 10	1		ENSP00000424497.1
SH3RF2	ENST00000506591.1	n.*139C>G		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	0.074
Eigen_PC	Benign	-0.0047
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.80
MutPred		0.61		Gain of ubiquitination at K45 (P = 0.1047);Gain of ubiquitination at K45 (P = 0.1047);
MVP		0.87
MPC		0.64
ClinPred		1.0	D
GERP RS		-0.83
Varity_R		0.82
gMVP		0.74

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-145317633;