2-109129988-G-A

Position:

• chr2-109129988-G-A

Variant summary

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

The NM_001099289.3(SH3RF3):​c.448G>A​(p.Ala150Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000611 in 1,144,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: SH3RF3 NM_001099289.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.400

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08156106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3RF3	NM_001099289.3	c.448G>A	p.Ala150Thr	missense_variant	1/10	ENST00000309415.8
SH3RF3-AS1	NR_029193.1	n.132C>T		non_coding_transcript_exon_variant	1/1
SH3RF3	XM_011511109.3	c.448G>A	p.Ala150Thr	missense_variant	1/9
RANBP2	XM_047445367.1	c.8370+356942G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3RF3	ENST00000309415.8	c.448G>A	p.Ala150Thr	missense_variant	1/10	5	NM_001099289.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000611 AC: 7 AN: 1144804 Hom.: 0 Cov.: 32 AF XY: 0.00000363 AC XY: 2 AN XY: 550992

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: 0.00000626

Gnomad4 OTH exome AF: 0.00

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

May 25, 2022

The c.448G>A (p.A150T) alteration is located in exon (coding exon ) of the SH3RF3 gene. This alteration results from a G to A substitution at nucleotide position 448, causing the alanine (A) at amino acid position 150 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	0.078
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.020
Sift	Benign	0.62	T
Sift4G	Benign	0.40	T
Polyphen		0.18	B
Vest4		0.090
MutPred		0.24		Gain of glycosylation at A150 (P = 0.0136);
MVP		0.20
MPC		0.19
ClinPred		0.13	T
GERP RS		3.0
Varity_R		0.029
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: chr2-109746444;