1-220579453-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_018650.5(MARK1):c.151A>G(p.Thr51Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,613,984 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 1 hom. )
Consequence
MARK1
NM_018650.5 missense
NM_018650.5 missense
Scores
15
Clinical Significance
Conservation
PhyloP100: 0.218
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.020046055).
BS2
?
High AC in GnomAd at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARK1 | NM_018650.5 | c.151A>G | p.Thr51Ala | missense_variant | 2/18 | ENST00000366917.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARK1 | ENST00000366917.6 | c.151A>G | p.Thr51Ala | missense_variant | 2/18 | 1 | NM_018650.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152196Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.000267 AC: 67AN: 251104Hom.: 0 AF XY: 0.000310 AC XY: 42AN XY: 135696
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GnomAD4 exome AF: 0.000479 AC: 700AN: 1461788Hom.: 1 Cov.: 31 AF XY: 0.000473 AC XY: 344AN XY: 727208
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GnomAD4 genome ? AF: 0.000204 AC: 31AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74344
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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 | Jan 23, 2023 | The c.151A>G (p.T51A) alteration is located in exon 2 (coding exon 2) of the MARK1 gene. This alteration results from a A to G substitution at nucleotide position 151, causing the threonine (T) at amino acid position 51 to be replaced by an alanine (A). 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
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;T
Polyphen
0.0
.;B;B;B
Vest4
MVP
MPC
0.86
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at