5-145938171-C-A

Variant names:

• chr5-145938171-C-A
• rs534789556
• NM_152550.4:c.243C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152550.4(SH3RF2):​c.243C>A​(p.Ser81Arg) 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 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• 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: 1.16
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07503101).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3RF2	NM_152550.4	MANE Select	c.243C>A	p.Ser81Arg	missense	Exon 2 of 10	NP_689763.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3RF2	ENST00000359120.9	TSL:1 MANE Select	c.243C>A	p.Ser81Arg	missense	Exon 2 of 10	ENSP00000352028.4	Q8TEC5-1
	SH3RF2	ENST00000511217.1	TSL:1	c.243C>A	p.Ser81Arg	missense	Exon 1 of 10	ENSP00000424497.1	Q8TEC5-1
	SH3RF2	ENST00000859825.1		c.243C>A	p.Ser81Arg	missense	Exon 2 of 11	ENSP00000529884.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461768 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.64
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.078
Sift	Benign	0.18	T
Sift4G	Benign	0.36	T
Polyphen		0.0040	B
Vest4		0.19
MutPred		0.28		Loss of phosphorylation at S81 (P = 0.0125)
MVP		0.25
MPC		0.13
ClinPred		0.20	T
GERP RS		5.2
PromoterAI		-0.0095	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.085
gMVP		0.37
Mutation Taster		=90/10	polymorphism

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: rs534789556; hg19: chr5-145317734; COSMIC: COSV108201626; COSMIC: COSV108201626;