chr5-145938233-G-C

Variant names:

• chr5-145938233-G-C
• rs1388290172
• NM_152550.4:c.305G>C

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.305G>C​(p.Ser102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH3RF2 NM_152550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• 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=0.07612991).

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.305G>C	p.Ser102Thr	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.305G>C	p.Ser102Thr	missense	Exon 2 of 10	ENSP00000352028.4	Q8TEC5-1
	SH3RF2	ENST00000511217.1	TSL:1	c.305G>C	p.Ser102Thr	missense	Exon 1 of 10	ENSP00000424497.1	Q8TEC5-1
	SH3RF2	ENST00000859825.1		c.305G>C	p.Ser102Thr	missense	Exon 2 of 11	ENSP00000529884.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.61
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.016
Sift	Benign	0.39	T
Sift4G	Benign	0.61	T
Polyphen		0.0030	B
Vest4		0.14
MutPred		0.27		Loss of ubiquitination at K101 (P = 0.0821)
MVP		0.27
MPC		0.11
ClinPred		0.038	T
GERP RS		3.1
PromoterAI		0.0054	Neutral
Varity_R		0.033
gMVP		0.32
Mutation Taster		=95/5	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: rs1388290172; hg19: chr5-145317796;