rs749544058

Variant names:

• chr5-145938244-C-G
• rs749544058
• NM_152550.4:c.316C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-145938244-C-G
• chr5-145938244-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152550.4(SH3RF2):​c.316C>G​(p.Pro106Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. P106S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SH3RF2 NM_152550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11904335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF2	NM_152550.4	c.316C>G	p.Pro106Ala	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.316C>G	p.Pro106Ala	missense_variant	Exon 2 of 10	1	NM_152550.4	ENSP00000352028.4
SH3RF2	ENST00000511217.1	c.316C>G	p.Pro106Ala	missense_variant	Exon 1 of 10	1		ENSP00000424497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456102 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724390

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.053	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.053
Sift	Benign	0.12	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.0	B;B
Vest4		0.28
MutPred		0.27		Loss of glycosylation at P106 (P = 0.02);Loss of glycosylation at P106 (P = 0.02);
MVP		0.36
MPC		0.12
ClinPred		0.061	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs749544058; hg19: chr5-145317807;