7-44002800-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001378423.2(SPDYE1):​c.590C>T​(p.Ala197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,522,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., cov: 15)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SPDYE1
NM_001378423.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110
Variant links:
Genes affected
SPDYE1 (HGNC:16408): (speedy/RINGO cell cycle regulator family member E1) This gene is located at chromosome 7p13 which is close to the Williams Beuren syndrome chromosome region 7q11.23. [provided by RefSeq, Jul 2008]
POLR2J4 (HGNC:28195): (RNA polymerase II subunit J4 (pseudogene))

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPDYE1NM_001378423.2 linkc.590C>T p.Ala197Val missense_variant Exon 4 of 9 ENST00000693451.1 NP_001365352.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPDYE1ENST00000693451.1 linkc.590C>T p.Ala197Val missense_variant Exon 4 of 9 NM_001378423.2 ENSP00000509569.1 A0A494C1S0

Frequencies

GnomAD3 genomes
AF:
0.00000926
AC:
1
AN:
108002
Hom.:
0
Cov.:
15
show subpopulations
Gnomad AFR
AF:
0.0000362
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:
0.0000251
AC:
5
AN:
198846
Hom.:
0
AF XY:
0.0000276
AC XY:
3
AN XY:
108560
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000189
GnomAD4 exome
AF:
0.0000269
AC:
38
AN:
1414804
Hom.:
0
Cov.:
28
AF XY:
0.0000270
AC XY:
19
AN XY:
702658
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000339
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.00000926
AC:
1
AN:
108002
Hom.:
0
Cov.:
15
AF XY:
0.0000199
AC XY:
1
AN XY:
50218
show subpopulations
Gnomad4 AFR
AF:
0.0000362
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
ExAC
AF:
0.0000339
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.470C>T (p.A157V) alteration is located in exon 2 (coding exon 2) of the SPDYE1 gene. This alteration results from a C to T substitution at nucleotide position 470, causing the alanine (A) at amino acid position 157 to be replaced by a valine (V). 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
0.20
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
8.8
DANN
Benign
0.78
DEOGEN2
Benign
0.0064
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.00076
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.045
Sift
Benign
0.25
T
Sift4G
Benign
0.24
T
Polyphen
0.68
P
Vest4
0.23
MutPred
0.27
Loss of disorder (P = 0.1573);
MVP
0.088
MPC
1.7
ClinPred
0.082
T
Varity_R
0.040
gMVP
0.069

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.24
Position offset: -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: rs764948935; hg19: chr7-44042399; API