rs17679127

chr14-103423754-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MARK3	NM_001128918.3	c.244-4633A>G		intron_variant		ENST00000429436.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK3	ENST00000429436.7	c.244-4633A>G		intron_variant		1	NM_001128918.3	P1

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

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0407

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.107

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

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: rs17679127; hg19: chr14-103890091;