7-44001173-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378423.2(SPDYE1):​c.268C>A​(p.Pro90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,446,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

SPDYE1
NM_001378423.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.636
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2001343).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPDYE1NM_001378423.2 linkc.268C>A p.Pro90Thr missense_variant Exon 3 of 9 ENST00000693451.1 NP_001365352.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPDYE1ENST00000693451.1 linkc.268C>A p.Pro90Thr missense_variant Exon 3 of 9 NM_001378423.2 ENSP00000509569.1 A0A494C1S0

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
AF:
0.00000277
AC:
4
AN:
1446296
Hom.:
0
Cov.:
34
AF XY:
0.00000278
AC XY:
2
AN XY:
719870
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.148C>A (p.P50T) alteration is located in exon 1 (coding exon 1) of the SPDYE1 gene. This alteration results from a C to A substitution at nucleotide position 148, causing the proline (P) at amino acid position 50 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
0.091
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.069
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.11
Sift
Uncertain
0.0020
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.043
MutPred
0.26
Loss of glycosylation at P50 (P = 0.0304);
MVP
0.11
MPC
2.6
ClinPred
0.92
D
Varity_R
0.18
gMVP
0.028

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-44040772; API