Variant 1-32335105-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_023009.7(MARCKSL1):c.88-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 1,519,726 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 39 hom. )

Consequence

MARCKSL1
NM_023009.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004764

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.05

Variant links:

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]

MARCKSL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-32335105-G-A is Benign according to our data. Variant chr1-32335105-G-A is described in ClinVar as [Benign]. Clinvar id is 731485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCKSL1	NM_023009.7 linkuse as main transcript	c.88-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000329421.8	NP_075385.1
MARCKSL1	NR_052852.2 linkuse as main transcript	n.63-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCKSL1	ENST00000329421.8 linkuse as main transcript	c.88-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_023009.7	ENSP00000362638	P1

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00741

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00468

AC:

825

AN:

176208

Hom.:

AF XY:

0.00490

AC XY:

456

AN XY:

93148

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.000287

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00185

Gnomad FIN exome

AF:

0.00386

Gnomad NFE exome

AF:

0.00712

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00695

AC:

9505

AN:

1367418

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

4495

AN XY:

670494

show subpopulations

Gnomad4 AFR exome

AF:

0.00109

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.0000502

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.00530

Gnomad4 NFE exome

AF:

0.00810

Gnomad4 OTH exome

AF:

0.00557

GnomAD4 genome

AF:

0.00437

AC:

666

AN:

152308

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.00741

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00630

Hom.:

Bravo

AF:

0.00450

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000048

dbscSNV1_RF

Benign

0.050

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

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