rs1175917747

Variant names:

• chr1-32335048-C-T
• rs1175917747
• NM_023009.7:c.137G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023009.7(MARCKSL1):​c.137G>A​(p.Gly46Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,914 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MARCKSL1 NM_023009.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 0 publications found

Genes affected

MARCKSL1 (HGNC:7142): (MARCKS like 1) This gene encodes a member of the myristoylated alanine-rich C-kinase substrate (MARCKS) family. Members of this family play a role in cytoskeletal regulation, protein kinase C signaling and calmodulin signaling. The encoded protein affects the formation of adherens junction. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are located on the long arm of chromosomes 6 and 10. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13472447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023009.7. 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
	MARCKSL1	NM_023009.7	MANE Select	c.137G>A	p.Gly46Glu	missense	Exon 2 of 2	NP_075385.1	P49006
	MARCKSL1	NR_052852.2		n.112G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCKSL1	ENST00000329421.8	TSL:1 MANE Select	c.137G>A	p.Gly46Glu	missense	Exon 2 of 2	ENSP00000362638.4	P49006
	MARCKSL1	ENST00000853128.1		c.560G>A	p.Gly187Glu	missense	Exon 2 of 2	ENSP00000523187.1
	MARCKSL1	ENST00000932579.1		c.134G>A	p.Gly45Glu	missense	Exon 2 of 2	ENSP00000602638.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406914 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 695876

African (AFR) AF: 0.00 AC: 0 AN: 31154

American (AMR) AF: 0.00 AC: 0 AN: 34616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22238

East Asian (EAS) AF: 0.00 AC: 0 AN: 39256

South Asian (SAS) AF: 0.00 AC: 0 AN: 78870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086394

Other (OTH) AF: 0.00 AC: 0 AN: 57740

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.078
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.017	D
Polyphen		0.11	B
Vest4		0.33
MutPred		0.16		Gain of solvent accessibility (P = 0.024)
MVP		0.043
MPC		0.70
ClinPred		0.99	D
GERP RS		3.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.64
gMVP		0.38
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1175917747; hg19: chr1-32800649;