chr15-83588697-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003027.5(SH3GL3):c.764A>G(p.Tyr255Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SH3GL3
NM_003027.5 missense
NM_003027.5 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 1.15
Genes affected
SH3GL3 (HGNC:10832): (SH3 domain containing GRB2 like 3, endophilin A3) Enables identical protein binding activity. Predicted to be involved in synaptic vesicle uncoating. Predicted to be located in acrosomal vesicle; early endosome membrane; and presynapse. Predicted to be part of early endosome. Predicted to be active in glutamatergic synapse; postsynaptic density, intracellular component; and postsynaptic endosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09294066).
BS2
?
High AC in GnomAdExome at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3GL3 | NM_003027.5 | c.764A>G | p.Tyr255Cys | missense_variant | 8/9 | ENST00000427482.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3GL3 | ENST00000427482.7 | c.764A>G | p.Tyr255Cys | missense_variant | 8/9 | 1 | NM_003027.5 | P1 | |
SH3GL3 | ENST00000563901.5 | c.*559A>G | 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 1 | ||||
SH3GL3 | ENST00000324537.5 | c.788A>G | p.Tyr263Cys | missense_variant | 11/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152252Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251450Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135898
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460604Hom.: 0 Cov.: 28 AF XY: 0.0000193 AC XY: 14AN XY: 726754
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74518
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.764A>G (p.Y255C) alteration is located in exon 8 (coding exon 8) of the SH3GL3 gene. This alteration results from a A to G substitution at nucleotide position 764, causing the tyrosine (Y) at amino acid position 255 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at