14-103417296-G-T

Variant names:

• chr14-103417296-G-T
• rs11623869
• NM_001128918.3:c.244-11091G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 48 publications found

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 Gene-Disease associations (from GenCC):

• visual impairment and progressive phthisis bulbi

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128918.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK3	NM_001128918.3	MANE Select	c.244-11091G>T		intron	N/A	NP_001122390.2
	MARK3	NM_001128919.3		c.244-11091G>T		intron	N/A	NP_001122391.2
	MARK3	NM_001437366.1		c.243+12029G>T		intron	N/A	NP_001424295.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK3	ENST00000429436.7	TSL:1 MANE Select	c.244-11091G>T		intron	N/A	ENSP00000411397.2
	MARK3	ENST00000556744.2	TSL:1	c.244-11091G>T		intron	N/A	ENSP00000451623.2
	MARK3	ENST00000416682.6	TSL:1	c.244-11091G>T		intron	N/A	ENSP00000408092.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.186 AC: 7688 AN: 41444

American (AMR) AF: 0.261 AC: 3977 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1559 AN: 3470

East Asian (EAS) AF: 0.143 AC: 741 AN: 5176

South Asian (SAS) AF: 0.337 AC: 1621 AN: 4812

European-Finnish (FIN) AF: 0.281 AC: 2953 AN: 10526

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 24022 AN: 67922

Other (OTH) AF: 0.319 AC: 673 AN: 2110

Alfa AF: 0.333 Hom.: 23487

Bravo AF: 0.279

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11623869; hg19: chr14-103883633;