Variant 6-109691304-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014845.6(FIG4):c.-132A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 753,100 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 1 hom. )

Consequence

FIG4
NM_014845.6 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

FIG4 (HGNC:16873): (FIG4 phosphoinositide 5-phosphatase) The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]

FIG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIG4	NM_014845.6 linkuse as main transcript	c.-132A>G		5_prime_UTR_variant	1/23	ENST00000230124.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIG4	ENST00000230124.8 linkuse as main transcript	c.-132A>G		5_prime_UTR_variant	1/23	1	NM_014845.6	P4

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

220

AN:

151034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000244

Gnomad AMI

AF:

0.0398

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.0000955

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00193

GnomAD4 exome

AF:

0.00167

AC:

1006

AN:

601950

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

548

AN XY:

321764

show subpopulations

Gnomad4 AFR exome

AF:

0.000365

Gnomad4 AMR exome

AF:

0.000412

Gnomad4 ASJ exome

AF:

0.000761

Gnomad4 EAS exome

AF:

0.0000627

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.000119

Gnomad4 NFE exome

AF:

0.00220

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00146

AC:

220

AN:

151150

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

101

AN XY:

73842

show subpopulations

Gnomad4 AFR

AF:

0.000243

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00147

Gnomad4 FIN

AF:

0.0000955

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.00148

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 11

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Charcot-Marie-Tooth disease type 4J

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.30

Dann

Benign

0.46

Splicing

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