6-113860125-G-GTGAGGC

Position:

• chr6-113860125-G-GTGAGGC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_002356.7(MARCKS):​c.552_557dup​(p.Glu185_Ala186dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,536,544 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0051 (22 hom.)
• Consequence: MARCKS NM_002356.7 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_002356.7.
• BP6: Variant 6-113860125-G-GTGAGGC is Benign according to our data. Variant chr6-113860125-G-GTGAGGC is described in ClinVar as [Benign]. Clinvar id is 774449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCKS	NM_002356.7	c.552_557dup	p.Glu185_Ala186dup	inframe_insertion	2/2	ENST00000612661.2	NP_002347.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCKS	ENST00000612661.2	c.552_557dup	p.Glu185_Ala186dup	inframe_insertion	2/2	1	NM_002356.7	ENSP00000478061	P1

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 583 AN: 149200 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.000997

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00166

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00592

Gnomad OTH AF: 0.000486

GnomAD3 exomes AF: 0.00321 AC: 606 AN: 188844 Hom.: 3 AF XY: 0.00319 AC XY: 341 AN XY: 106994

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.000560

Gnomad ASJ exome AF: 0.000239

Gnomad EAS exome AF: 0.000277

Gnomad SAS exome AF: 0.000388

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.00412

Gnomad OTH exome AF: 0.00189

GnomAD4 exome AF: 0.00511 AC: 7083 AN: 1387244 Hom.: 22 Cov.: 34 AF XY: 0.00486 AC XY: 3357 AN XY: 690848

Gnomad4 AFR exome AF: 0.000912

Gnomad4 AMR exome AF: 0.000772

Gnomad4 ASJ exome AF: 0.0000426

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.00576

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.00390 AC: 583 AN: 149300 Hom.: 5 Cov.: 31 AF XY: 0.00372 AC XY: 271 AN XY: 72862

Gnomad4 AFR AF: 0.000995

Gnomad4 AMR AF: 0.00166

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.00592

Gnomad4 OTH AF: 0.000481

Alfa AF: 0.00483 Hom.: 3

Bravo AF: 0.00307

Asia WGS AF: 0.000593 AC: 2 AN: 3388

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 09, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs747922228; hg19: chr6-114181301;