6-109732621-GT-GTTT

Position:

• chr6-109732621-GT-GTTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000230124.8(FIG4):​c.447-4_447-3dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (17 hom., cov: 0)
  • Exomes 𝑓: 0.11 (5 hom.)
• Consequence: FIG4 ENST00000230124.8 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0950

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-109732621-G-GTT is Benign according to our data. Variant chr6-109732621-G-GTT is described in ClinVar as [Likely_benign]. Clinvar id is 917084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIG4	NM_014845.6	c.447-4_447-3dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000230124.8	NP_055660.1
FIG4	XM_011536281.4	c.384-4_384-3dup		splice_polypyrimidine_tract_variant, intron_variant			XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8	c.447-4_447-3dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014845.6	ENSP00000230124	P4

Frequencies

GnomAD3 genomes AF: 0.00958 AC: 1410 AN: 147222 Hom.: 17 Cov.: 0

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00637

Gnomad ASJ AF: 0.00262

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00551

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00697

GnomAD4 exome AF: 0.114 AC: 91472 AN: 800370 Hom.: 5 Cov.: 17 AF XY: 0.113 AC XY: 46895 AN XY: 413228

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.00964 AC: 1420 AN: 147268 Hom.: 17 Cov.: 0 AF XY: 0.00960 AC XY: 687 AN XY: 71538

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.00636

Gnomad4 ASJ AF: 0.00262

Gnomad4 EAS AF: 0.00158

Gnomad4 SAS AF: 0.00107

Gnomad4 FIN AF: 0.00551

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00692

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 06, 2019	- -

Charcot-Marie-Tooth disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

-

- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

-

- -

Charcot-Marie-Tooth disease type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

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: rs11377100; hg19: chr6-110053824;