1-220635393-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018650.5(MARK1):c.1140G>A(p.Ser380=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,598,858 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: MARK1 NM_018650.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.08

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-220635393-G-A is Benign according to our data. Variant chr1-220635393-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.08 with no splicing effect.
• BS2: High AC in GnomAd at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARK1	NM_018650.5	c.1140G>A	p.Ser380=	synonymous_variant	12/18	ENST00000366917.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK1	ENST00000366917.6	c.1140G>A	p.Ser380=	synonymous_variant	12/18	1	NM_018650.5	P3

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 60 AN: 147134 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.000322

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000785

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000319 AC: 78 AN: 244168 Hom.: 0 AF XY: 0.000205 AC XY: 27 AN XY: 132026

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000347

Gnomad FIN exome AF: 0.000419

Gnomad NFE exome AF: 0.000565

Gnomad OTH exome AF: 0.000505

GnomAD4 exome AF: 0.000251 AC: 364 AN: 1451724 Hom.: 1 Cov.: 36 AF XY: 0.000273 AC XY: 197 AN XY: 722106

Gnomad4 AFR exome AF: 0.0000607

Gnomad4 AMR exome AF: 0.0000235

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.000263

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.000184

GnomAD4 genome AF: 0.000408 AC: 60 AN: 147134 Hom.: 0 Cov.: 29 AF XY: 0.000393 AC XY: 28 AN XY: 71280

Gnomad4 AFR AF: 0.0000506

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.000322

Gnomad4 NFE AF: 0.000785

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000716 Hom.: 0

Bravo AF: 0.000314

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

MARK1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	4.5
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs148023363; hg19: chr1-220808735; COSMIC: COSV65068727;