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GeneBe

1-220618528-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_018650.5(MARK1):c.771C>T(p.Phe257=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,992 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 8 hom. )

Consequence

MARK1
NM_018650.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53
Variant links:
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 -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-220618528-C-T is Benign according to our data. Variant chr1-220618528-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779300.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.53 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 211 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MARK1NM_018650.5 linkuse as main transcriptc.771C>T p.Phe257= synonymous_variant 8/18 ENST00000366917.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MARK1ENST00000366917.6 linkuse as main transcriptc.771C>T p.Phe257= synonymous_variant 8/181 NM_018650.5 P3Q9P0L2-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00139
AC:
211
AN:
152116
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000983
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00253
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00146
AC:
367
AN:
250712
Hom.:
1
AF XY:
0.00148
AC XY:
201
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.000820
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000883
Gnomad FIN exome
AF:
0.000462
Gnomad NFE exome
AF:
0.00240
Gnomad OTH exome
AF:
0.00115
GnomAD4 exome
AF:
0.00267
AC:
3900
AN:
1461758
Hom.:
8
Cov.:
31
AF XY:
0.00263
AC XY:
1914
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.00116
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000881
Gnomad4 FIN exome
AF:
0.000262
Gnomad4 NFE exome
AF:
0.00325
Gnomad4 OTH exome
AF:
0.00214
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00139
AC:
211
AN:
152234
Hom.:
1
Cov.:
33
AF XY:
0.00118
AC XY:
88
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000982
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00253
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00219
Hom.:
0
Bravo
AF:
0.00148
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00245
EpiControl
AF:
0.00160

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeApr 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
1.6
Dann
Benign
0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56188826; hg19: chr1-220791870; COSMIC: COSV100857532; API