Variant 6-113860131-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002356.7(MARCKS):c.551C>T(p.Ala184Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,502,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

MARCKS
NM_002356.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0260

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058593452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCKS	NM_002356.7 linkuse as main transcript	c.551C>T	p.Ala184Val	missense_variant	2/2	ENST00000612661.2	NP_002347.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCKS	ENST00000612661.2 linkuse as main transcript	c.551C>T	p.Ala184Val	missense_variant	2/2	1	NM_002356.7	ENSP00000478061	P1

Frequencies

GnomAD3 genomes

AF:

0.0000939

AC:

AN:

149074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000988

AC:

AN:

172142

Hom.:

AF XY:

0.0000711

AC XY:

AN XY:

98480

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000426

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.000153

Gnomad OTH exome

AF:

0.000533

GnomAD4 exome

AF:

0.000138

AC:

187

AN:

1353344

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

102

AN XY:

674298

show subpopulations

Gnomad4 AFR exome

AF:

0.0000371

Gnomad4 AMR exome

AF:

0.0000307

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.000125

Gnomad4 NFE exome

AF:

0.000161

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000939

AC:

AN:

149074

Hom.:

Cov.:

AF XY:

0.0000826

AC XY:

AN XY:

72654

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000208

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000349

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000942

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

Apr 26, 2023

The c.551C>T (p.A184V) alteration is located in exon 2 (coding exon 2) of the MARCKS gene. This alteration results from a C to T substitution at nucleotide position 551, causing the alanine (A) at amino acid position 184 to be replaced by a valine (V). 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

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.51

M_CAP

Benign

0.052

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

Sift4G

Uncertain

0.010

Polyphen

0.0010

Vest4

0.045

MutPred

0.43

Gain of sheet (P = 0.0061);

MVP

0.29

ClinPred

0.031

GERP RS

-0.57

Varity_R

0.11

gMVP

0.13

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