rs778866655

Variant summary

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

The NM_001394956.1(SPDYE4):​c.439G>T​(p.Gly147Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G147S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPDYE4
NM_001394956.1 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14
Variant links:
Genes affected
SPDYE4 (HGNC:35463): (speedy/RINGO cell cycle regulator family member E4) 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 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=0.36120385).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPDYE4NM_001394956.1 linkc.439G>T p.Gly147Cys missense_variant Exon 4 of 7 ENST00000689094.1 NP_001381885.1
SPDYE4NM_001128076.3 linkc.439G>T p.Gly147Cys missense_variant Exon 4 of 7 NP_001121548.1 A6NLX3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPDYE4ENST00000689094.1 linkc.439G>T p.Gly147Cys missense_variant Exon 4 of 7 NM_001394956.1 ENSP00000509506.1 A6NLX3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460208
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726358
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Uncertain
0.028
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
21
DANN
Benign
0.75
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.083
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.36
T
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Benign
0.20
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.32
MutPred
0.47
Loss of relative solvent accessibility (P = 0.107);
MVP
0.27
MPC
0.42
ClinPred
0.97
D
GERP RS
2.9
Varity_R
0.79
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: chr17-8658884; API