rs17679127

Variant names:

• chr14-103423754-A-G
• rs17679127
• NM_001128918.3:c.244-4633A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128918.3(MARK3):​c.244-4633A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,280 control chromosomes in the GnomAD database, including 1,047 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 0.10 (1047 hom., cov: 31)
• Consequence: MARK3 NM_001128918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARK3	NM_001128918.3	c.244-4633A>G		intron_variant	Intron 2 of 17	ENST00000429436.7	NP_001122390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARK3	ENST00000429436.7	c.244-4633A>G		intron_variant	Intron 2 of 17	1	NM_001128918.3	ENSP00000411397.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15841 AN: 152162 Hom.: 1051 Cov.: 31

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15833 AN: 152280 Hom.: 1047 Cov.: 31 AF XY: 0.104 AC XY: 7751 AN XY: 74446

African (AFR) AF: 0.0369 AC: 1532 AN: 41566

American (AMR) AF: 0.0998 AC: 1527 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3466

East Asian (EAS) AF: 0.0407 AC: 211 AN: 5184

South Asian (SAS) AF: 0.181 AC: 874 AN: 4828

European-Finnish (FIN) AF: 0.117 AC: 1246 AN: 10608

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9511 AN: 68012

Other (OTH) AF: 0.107 AC: 227 AN: 2116

Alfa AF: 0.125 Hom.: 237

Bravo AF: 0.0959

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.66
PhyloP100		0.21
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: rs17679127; hg19: chr14-103890091;