2-109129771-C-G

Position:

• chr2-109129771-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001099289.3(SH3RF3):​c.231C>G​(p.Phe77Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3RF3 NM_001099289.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

Genes affected

SH3RF3 (HGNC:24699): (SH3 domain containing ring finger 3) Enables ubiquitin protein ligase activity. Involved in positive regulation of JNK cascade and protein autoubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

SH3RF3-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3RF3	NM_001099289.3	c.231C>G	p.Phe77Leu	missense_variant	1/10	ENST00000309415.8
SH3RF3-AS1	NR_029193.1	n.349G>C		non_coding_transcript_exon_variant	1/1
SH3RF3	XM_011511109.3	c.231C>G	p.Phe77Leu	missense_variant	1/9
RANBP2	XM_047445367.1	c.8370+356725C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3RF3	ENST00000309415.8	c.231C>G	p.Phe77Leu	missense_variant	1/10	5	NM_001099289.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Dec 16, 2023

The c.231C>G (p.F77L) alteration is located in exon (coding exon ) of the SH3RF3 gene. This alteration results from a C to G substitution at nucleotide position 231, causing the phenylalanine (F) at amino acid position 77 to be replaced by a leucine (L). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.76	D
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.96	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.86		Gain of disorder (P = 0.0418);
MVP		0.76
MPC		0.82
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.77
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: chr2-109746227;