14-103417296-G-T

Position:

• chr14-103417296-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128918.3(MARK3):​c.244-11091G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,924 control chromosomes in the GnomAD database, including 6,851 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6851 hom., cov: 31)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: MARK3 NM_001128918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

Genes affected

MARK3 (HGNC:6897): (microtubule affinity regulating kinase 3) The protein encoded by this gene is activated by phosphorylation and in turn is involved in the phosphorylation of tau proteins MAP2 and MAP4. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

MARK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARK3	NM_001128918.3	c.244-11091G>T		intron_variant		ENST00000429436.7	NP_001122390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARK3	ENST00000429436.7	c.244-11091G>T		intron_variant		1	NM_001128918.3	ENSP00000411397.2

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43618 AN: 151798 Hom.: 6853 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.287 AC: 43616 AN: 151916 Hom.: 6851 Cov.: 31 AF XY: 0.284 AC XY: 21071 AN XY: 74240

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.319

Alfa AF: 0.331 Hom.: 7342

Bravo AF: 0.279

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.70

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: rs11623869; hg19: chr14-103883633;