1-220635836-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018650.5(MARK1):c.1280G>A(p.Gly427Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
MARK1
NM_018650.5 missense
NM_018650.5 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 7.22
Genes affected
MARK1 (HGNC:6896): (microtubule affinity regulating kinase 1) Enables several functions, including ATP binding activity; phospholipid binding activity; and protein kinase activity. Involved in intracellular signal transduction and protein phosphorylation. Located in cytoplasm; dendrite; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MARK1 | NM_018650.5 | c.1280G>A | p.Gly427Asp | missense_variant | 13/18 | ENST00000366917.6 | NP_061120.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MARK1 | ENST00000366917.6 | c.1280G>A | p.Gly427Asp | missense_variant | 13/18 | 1 | NM_018650.5 | ENSP00000355884 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 30
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74304
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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 | Feb 27, 2023 | The c.1280G>A (p.G427D) alteration is located in exon 13 (coding exon 13) of the MARK1 gene. This alteration results from a G to A substitution at nucleotide position 1280, causing the glycine (G) at amino acid position 427 to be replaced by an aspartic acid (D). 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
Benign
T;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;.;D;D
REVEL
Benign
Sift
Uncertain
.;.;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.85, 0.99, 0.98
.;P;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);.;Loss of MoRF binding (P = 0.0577);
MVP
MPC
0.71
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 37
Find out detailed SpliceAI scores and Pangolin per-transcript scores at