Variant chr6-113859923-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000612661.2(MARCKS):c.343G>A(p.Glu115Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,466,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E115D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MARCKS
ENST00000612661.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Variant links:

Genes affected

MARCKS (HGNC:6759): (myristoylated alanine rich protein kinase C substrate) The protein encoded by this gene is a substrate for protein kinase C. It is localized to the plasma membrane and is an actin filament crosslinking protein. Phosphorylation by protein kinase C or binding to calcium-calmodulin inhibits its association with actin and with the plasma membrane, leading to its presence in the cytoplasm. The protein is thought to be involved in cell motility, phagocytosis, membrane trafficking and mitogenesis. [provided by RefSeq, Jul 2008]

MARCKS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32458904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCKS	NM_002356.7 linkuse as main transcript	c.343G>A	p.Glu115Lys	missense_variant	2/2	ENST00000612661.2	NP_002347.5	P29966Q6NVI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCKS	ENST00000612661.2 linkuse as main transcript	c.343G>A	p.Glu115Lys	missense_variant	2/2	1	NM_002356.7	ENSP00000478061.1		P29966

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1316318

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

650018

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000539

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000134

Gnomad4 OTH exome

AF:

0.0000371

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73210

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000203

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.343G>A (p.E115K) alteration is located in exon 2 (coding exon 2) of the MARCKS gene. This alteration results from a G to A substitution at nucleotide position 343, causing the glutamic acid (E) at amino acid position 115 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Benign

0.16

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.92

Sift4G

Benign

0.44

Polyphen

0.95

Vest4

0.25

MutPred

0.47

Gain of methylation at E115 (P = 0.0071);

MVP

0.45

ClinPred

0.85

GERP RS

2.3

Varity_R

0.13

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over