rs927071746

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020870.4(SH3RF1):​c.2233G>C​(p.Glu745Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E745K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SH3RF1
NM_020870.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.18
Variant links:
Genes affected
SH3RF1 (HGNC:17650): (SH3 domain containing ring finger 1) This gene encodes a protein containing an N-terminus RING-finger, four SH3 domains, and a region implicated in binding of the Rho GTPase Rac. Via the RING-finger, the encoded protein has been shown to function as an ubiquitin-protein ligase involved in protein sorting at the trans-Golgi network. The encoded protein may also act as a scaffold for the c-Jun N-terminal kinase signaling pathway, facilitating the formation of a functional signaling module. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36591282).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH3RF1NM_020870.4 linkc.2233G>C p.Glu745Gln missense_variant Exon 11 of 12 ENST00000284637.14 NP_065921.2 Q7Z6J0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH3RF1ENST00000284637.14 linkc.2233G>C p.Glu745Gln missense_variant Exon 11 of 12 1 NM_020870.4 ENSP00000284637.9 Q7Z6J0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.28
N
REVEL
Benign
0.18
Sift
Benign
0.70
T
Sift4G
Benign
0.44
T
Polyphen
1.0
D
Vest4
0.39
MutPred
0.20
Loss of phosphorylation at S748 (P = 0.1065);
MVP
0.56
MPC
0.63
ClinPred
0.92
D
GERP RS
5.9
Varity_R
0.11
gMVP
0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs927071746; hg19: chr4-170028263; API