rs56134485

Variant names:

• chr14-103475042-C-A
• rs56134485
• NM_001128918.3:c.1314C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_001128918.3(MARK3):​c.1314C>A​(p.Thr438Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,614,042 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.044 (512 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (437 hom.)
• Consequence: MARK3 NM_001128918.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.06
• Publications: 1 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: AR, Unknown Classification: LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.035).
• BP6: Variant 14-103475042-C-A is Benign according to our data. Variant chr14-103475042-C-A is described in ClinVar as Benign. ClinVar VariationId is 3055758.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK3	NM_001128918.3	MANE Select	c.1314C>A	p.Thr438Thr	synonymous	Exon 13 of 18	NP_001122390.2	P27448-5
	MARK3	NM_001128919.3		c.1314C>A	p.Thr438Thr	synonymous	Exon 13 of 17	NP_001122391.2	P27448-4
	MARK3	NM_001437366.1		c.1260C>A	p.Thr420Thr	synonymous	Exon 12 of 17	NP_001424295.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK3	ENST00000429436.7	TSL:1 MANE Select	c.1314C>A	p.Thr438Thr	synonymous	Exon 13 of 18	ENSP00000411397.2	P27448-5
	MARK3	ENST00000556744.2	TSL:1	c.1266C>A	p.Thr422Thr	synonymous	Exon 13 of 19	ENSP00000451623.2	H0YJI9
	MARK3	ENST00000416682.6	TSL:1	c.1383C>A	p.Thr461Thr	synonymous	Exon 14 of 17	ENSP00000408092.2	P27448-2

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6632 AN: 152120 Hom.: 510 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.0108 AC: 2686 AN: 249504 AF XY: 0.00790

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.00678

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00363

GnomAD4 exome AF: 0.00427 AC: 6236 AN: 1461804 Hom.: 437 Cov.: 31 AF XY: 0.00363 AC XY: 2641 AN XY: 727216

African (AFR) AF: 0.155 AC: 5179 AN: 33424

American (AMR) AF: 0.00776 AC: 347 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.0000818 AC: 91 AN: 1111994

Other (OTH) AF: 0.00947 AC: 572 AN: 60386

GnomAD4 genome AF: 0.0437 AC: 6649 AN: 152238 Hom.: 512 Cov.: 33 AF XY: 0.0416 AC XY: 3095 AN XY: 74438

African (AFR) AF: 0.154 AC: 6377 AN: 41524

American (AMR) AF: 0.0134 AC: 205 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68018

Other (OTH) AF: 0.0203 AC: 43 AN: 2114

Alfa AF: 0.0199 Hom.: 140

Bravo AF: 0.0494

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MARK3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.7
DANN	Benign	0.41
PhyloP100		1.1
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: rs56134485; hg19: chr14-103941379;