5-145938233-G-C

Position:

• chr5-145938233-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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=0.07612991).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3RF2	NM_152550.4	c.305G>C	p.Ser102Thr	missense_variant	2/10	ENST00000359120.9	NP_689763.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3RF2	ENST00000359120.9	c.305G>C	p.Ser102Thr	missense_variant	2/10	1	NM_152550.4	ENSP00000352028.4
SH3RF2	ENST00000511217.1	c.305G>C	p.Ser102Thr	missense_variant	1/10	1		ENSP00000424497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.305G>C (p.S102T) alteration is located in exon 2 (coding exon 1) of the SH3RF2 gene. This alteration results from a G to C substitution at nucleotide position 305, causing the serine (S) at amino acid position 102 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.016
Sift	Benign	0.39	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.0030	B;B
Vest4		0.14
MutPred		0.27		Loss of ubiquitination at K101 (P = 0.0821);Loss of ubiquitination at K101 (P = 0.0821);
MVP		0.27
MPC		0.11
ClinPred		0.038	T
GERP RS		3.1
Varity_R		0.033
gMVP		0.32

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: chr5-145317796;