1-220616013-ATT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_018650.5(MARK1):c.552+24_552+25del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,027,666 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: MARK1 NM_018650.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-220616013-ATT-A is Benign according to our data. Variant chr1-220616013-ATT-A is described in ClinVar as [Benign]. Clinvar id is 2776120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARK1	NM_018650.5	c.552+24_552+25del		intron_variant		ENST00000366917.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK1	ENST00000366917.6	c.552+24_552+25del		intron_variant		1	NM_018650.5	P3

Frequencies

GnomAD3 genomes AF: 0.000285 AC: 43 AN: 150858 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00426

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000196

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00149 AC: 1309 AN: 876704 Hom.: 1 AF XY: 0.00144 AC XY: 648 AN XY: 450906

Gnomad4 AFR exome AF: 0.000548

Gnomad4 AMR exome AF: 0.00149

Gnomad4 ASJ exome AF: 0.000533

Gnomad4 EAS exome AF: 0.0113

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.00102

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.00143

GnomAD4 genome AF: 0.000285 AC: 43 AN: 150962 Hom.: 0 Cov.: 25 AF XY: 0.000312 AC XY: 23 AN XY: 73702

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00427

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000196

Gnomad4 NFE AF: 0.000251

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00443 Hom.: 425

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

Nov 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs67564055; hg19: chr1-220789355;