19-45825259-T-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004819.3(SYMPK):c.2402A>T(p.Asn801Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
SYMPK
NM_004819.3 missense
NM_004819.3 missense
Scores
6
12
1
Clinical Significance
Conservation
PhyloP100: 5.68
Genes affected
SYMPK (HGNC:22935): (symplekin scaffold protein) This gene encodes a nuclear protein that functions in the regulation of polyadenylation and promotes gene expression. The protein forms a high-molecular weight complex with components of the polyadenylation machinery. It is thought to serve as a scaffold for recruiting regulatory factors to the polyadenylation complex. It also participates in 3'-end maturation of histone mRNAs, which do not undergo polyadenylation. The protein also localizes to the cytoplasmic plaques of tight junctions in some cell types. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.79
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYMPK | NM_004819.3 | c.2402A>T | p.Asn801Ile | missense_variant | 18/27 | ENST00000245934.12 | |
SYMPK | XM_011527354.2 | c.2402A>T | p.Asn801Ile | missense_variant | 19/28 | ||
SYMPK | XM_047439485.1 | c.2402A>T | p.Asn801Ile | missense_variant | 18/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYMPK | ENST00000245934.12 | c.2402A>T | p.Asn801Ile | missense_variant | 18/27 | 1 | NM_004819.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 | Dec 13, 2023 | The c.2402A>T (p.N801I) alteration is located in exon 18 (coding exon 17) of the SYMPK gene. This alteration results from a A to T substitution at nucleotide position 2402, causing the asparagine (N) at amino acid position 801 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.
Sift4G
Pathogenic
D;D;D
Polyphen
P;.;.
Vest4
MutPred
Gain of methylation at K803 (P = 0.0786);Gain of methylation at K803 (P = 0.0786);Gain of methylation at K803 (P = 0.0786);
MVP
MPC
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
DS_AG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.