chr2-231136-G-T

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015677.4(SH3YL1):​c.589C>A​(p.Pro197Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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

SH3YL1
NM_015677.4 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.06
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 made for transcript

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, 0.799

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH3YL1NM_015677.4 linkuse as main transcriptc.589C>A p.Pro197Thr missense_variant 7/10 ENST00000356150.10 NP_056492.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH3YL1ENST00000356150.10 linkuse as main transcriptc.589C>A p.Pro197Thr missense_variant 7/101 NM_015677.4 ENSP00000348471 P1Q96HL8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsApr 07, 2022The c.589C>A (p.P197T) alteration is located in exon 7 (coding exon 7) of the SH3YL1 gene. This alteration results from a C to A substitution at nucleotide position 589, causing the proline (P) at amino acid position 197 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
0.27
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.50
.;.;.;D;D;.;T;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;.;.;D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Pathogenic
0.80
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.55
T
MutationAssessor
Pathogenic
3.5
H;.;.;H;H;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-7.2
D;.;D;D;D;D;D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0020
D;.;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
.;D;D;.;.;D;D;D
Polyphen
1.0
D;D;D;D;D;D;.;.
Vest4
0.72
MutPred
0.57
Gain of phosphorylation at P197 (P = 0.0489);.;.;Gain of phosphorylation at P197 (P = 0.0489);Gain of phosphorylation at P197 (P = 0.0489);.;.;.;
MVP
0.55
MPC
0.47
ClinPred
1.0
D
GERP RS
4.2
Varity_R
0.69
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr2-231136; API