7-100310492-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004351.5(SPDYE3):​c.458C>T​(p.Thr153Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 4)
Exomes 𝑓: 0.000094 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

SPDYE3
NM_001004351.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.138
Variant links:
Genes affected
SPDYE3 (HGNC:35462): (speedy/RINGO cell cycle regulator family member E3) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.071035266).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPDYE3NM_001004351.5 linkc.458C>T p.Thr153Met missense_variant Exon 3 of 11 ENST00000332397.6 NP_001004351.3 A6NKU9-1
SPDYE3XM_047420404.1 linkc.458C>T p.Thr153Met missense_variant Exon 3 of 10 XP_047276360.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPDYE3ENST00000332397.6 linkc.458C>T p.Thr153Met missense_variant Exon 3 of 11 1 NM_001004351.5 ENSP00000329565.6 A6NKU9-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
14898
Hom.:
0
Cov.:
4
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000873
AC:
3
AN:
34366
Hom.:
0
AF XY:
0.000113
AC XY:
2
AN XY:
17746
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000161
Gnomad SAS exome
AF:
0.000230
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000935
AC:
34
AN:
363558
Hom.:
1
Cov.:
0
AF XY:
0.000130
AC XY:
25
AN XY:
192392
show subpopulations
Gnomad4 AFR exome
AF:
0.000193
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000770
Gnomad4 SAS exome
AF:
0.000518
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000331
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
14898
Hom.:
0
Cov.:
4
AF XY:
0.00
AC XY:
0
AN XY:
6358
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.458C>T (p.T153M) alteration is located in exon 3 (coding exon 3) of the SPDYE3 gene. This alteration results from a C to T substitution at nucleotide position 458, causing the threonine (T) at amino acid position 153 to be replaced by a methionine (M). 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
0.24
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
11
DANN
Benign
0.15
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.00067
T
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.036
Sift
Benign
0.41
T
Sift4G
Uncertain
0.0040
D
Vest4
0.21
MutPred
0.27
Gain of catalytic residue at T153 (P = 0.003);
MVP
0.043
MPC
1.7
ClinPred
0.011
T
GERP RS
0.17
Varity_R
0.034
gMVP
0.016

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: rs1467124465; hg19: chr7-99908115; API