GeneBe

rs10181051

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000626873.2(SH3YL1):​c.1A>T​(p.Met1?) variant causes a initiator codon, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SH3YL1
ENST00000626873.2 initiator_codon, splice_region

Scores

2
1
10
Splicing: ADA: 0.00004176
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

16 publications found
Variant links:
Genes affected
SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000626873.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SH3YL1
NM_015677.4
MANE Select
c.291+4738A>T
intron
N/ANP_056492.2
SH3YL1
NM_001282687.2
c.1A>Tp.Met1?
initiator_codon splice_region
Exon 6 of 12NP_001269616.1
SH3YL1
NM_001282682.2
c.1A>Tp.Met1?
initiator_codon splice_region
Exon 6 of 11NP_001269611.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SH3YL1
ENST00000626873.2
TSL:5
c.1A>Tp.Met1?
initiator_codon splice_region
Exon 7 of 13ENSP00000485824.1
SH3YL1
ENST00000356150.10
TSL:1 MANE Select
c.291+4738A>T
intron
N/AENSP00000348471.5
SH3YL1
ENST00000403712.6
TSL:1
c.291+4738A>T
intron
N/AENSP00000384276.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1383252
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
682278
African (AFR)
AF:
0.00
AC:
0
AN:
30990
American (AMR)
AF:
0.00
AC:
0
AN:
32962
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24828
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34322
South Asian (SAS)
AF:
0.00
AC:
0
AN:
76466
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48520
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5642
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1072216
Other (OTH)
AF:
0.00
AC:
0
AN:
57306
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
10
DANN
Benign
0.71
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.014
N
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.84
D
MetaSVM
Benign
-1.0
T
PhyloP100
0.21
PROVEAN
Benign
-0.90
N
REVEL
Benign
0.047
Sift
Pathogenic
0.0
D
Polyphen
0.011
B
Vest4
0.33
MutPred
0.85
Loss of disorder (P = 0.1186)
MVP
0.11
ClinPred
0.16
T
GERP RS
0.13
Mutation Taster
=84/116
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000042
dbscSNV1_RF
Benign
0.0
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

Other links and lift over

dbSNP: rs10181051; hg19: chr2-242800; API