1-220652035-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018650.5(MARK1):c.1621G>C(p.Ala541Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,612,592 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0093 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (70 hom.)
• Consequence: MARK1 NM_018650.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.83

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-220652035-G-C is Benign according to our data. Variant chr1-220652035-G-C is described in ClinVar as [Benign]. Clinvar id is 784970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00934 (1421/152132) while in subpopulation AFR AF= 0.0296 (1227/41478). AF 95% confidence interval is 0.0282. There are 31 homozygotes in gnomad4. There are 699 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1415 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARK1	NM_018650.5	c.1621G>C	p.Ala541Pro	missense_variant	15/18	ENST00000366917.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK1	ENST00000366917.6	c.1621G>C	p.Ala541Pro	missense_variant	15/18	1	NM_018650.5	P3

Frequencies

GnomAD3 genomes AF: 0.00931 AC: 1415 AN: 152014 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00504 AC: 1266 AN: 251324 Hom.: 25 AF XY: 0.00549 AC XY: 746 AN XY: 135838

Gnomad AFR exome AF: 0.0297

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00245

Gnomad SAS exome AF: 0.0213

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00224 AC: 3273 AN: 1460460 Hom.: 70 Cov.: 31 AF XY: 0.00267 AC XY: 1938 AN XY: 726462

Gnomad4 AFR exome AF: 0.0315

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000832

Gnomad4 SAS exome AF: 0.0211

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.00934 AC: 1421 AN: 152132 Hom.: 31 Cov.: 32 AF XY: 0.00940 AC XY: 699 AN XY: 74368

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.000917 Hom.: 3

Bravo AF: 0.00938

ESP6500AA AF: 0.0279 AC: 123

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00579 AC: 703

Asia WGS AF: 0.0230 AC: 79 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.52
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.010	T;.;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;T;T
MetaRNN	Benign	0.0038	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.56	T;T;T;T
Polyphen		0.0, 0.080	.;B;B;B
Vest4		0.42
MVP		0.16
MPC		0.26
ClinPred		0.010	T
GERP RS		2.4
Varity_R		0.062
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79027592; hg19: chr1-220825377;