1-67424242-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001018069.2(SERBP1):c.731C>A(p.Pro244His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
SERBP1
NM_001018069.2 missense
NM_001018069.2 missense
Scores
3
5
9
Clinical Significance
Conservation
PhyloP100: 7.42
Genes affected
SERBP1 (HGNC:17860): (SERPINE1 mRNA binding protein 1) Enables SUMO binding activity; mRNA 3'-UTR binding activity; and ribosome binding activity. Involved in PML body organization. Located in cytosol and nucleus. [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 -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28848094).
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERBP1 | NM_001018069.2 | c.731C>A | p.Pro244His | missense_variant | 5/8 | ENST00000361219.11 | |
SERBP1 | NM_001018067.2 | c.776C>A | p.Pro259His | missense_variant | 5/8 | ||
SERBP1 | NM_001018068.2 | c.758C>A | p.Pro253His | missense_variant | 5/8 | ||
SERBP1 | NM_015640.4 | c.713C>A | p.Pro238His | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERBP1 | ENST00000361219.11 | c.731C>A | p.Pro244His | missense_variant | 5/8 | 1 | NM_001018069.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152128Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
10
AN:
152128
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250054Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135194
GnomAD3 exomes
AF:
AC:
3
AN:
250054
Hom.:
AF XY:
AC XY:
2
AN XY:
135194
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460240Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726412
GnomAD4 exome
AF:
AC:
5
AN:
1460240
Hom.:
Cov.:
30
AF XY:
AC XY:
5
AN XY:
726412
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74302
GnomAD4 genome
?
AF:
AC:
10
AN:
152128
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
74302
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
3
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 submitter | clinical testing | Ambry Genetics | Jan 11, 2023 | The c.776C>A (p.P259H) alteration is located in exon 5 (coding exon 5) of the SERBP1 gene. This alteration results from a C to A substitution at nucleotide position 776, causing the proline (P) at amino acid position 259 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
1.0, 1.0
.;D;D;.
Vest4
MVP
MPC
0.21
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at