rs11377100

chr6-109732621-GT-Gchr6-109732621-GT-GTTchr6-109732621-GT-GTTTchr6-109732621-GT-GTTTTchr6-109732621-GT-GTTTTTchr6-109732621-GT-GTTTTTTchr6-109732621-GT-GTTTTTTTTTchr6-109732621-GT-GTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_014845.6(FIG4):c.447-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,008,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000088 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0043 (0 hom.)
• Consequence: FIG4 NM_014845.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 6-109732621-GT-G is Benign according to our data. Variant chr6-109732621-GT-G is described in ClinVar as [Benign]. Clinvar id is 1610293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-109732621-GT-G is described in Lovd as [Benign]. Variant chr6-109732621-GT-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIG4	NM_014845.6	c.447-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000230124.8
FIG4	XM_011536281.4	c.384-3del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000882 AC: 13 AN: 147342 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000677

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000898

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00428 AC: 3688 AN: 860780 Hom.: 0 Cov.: 17 AF XY: 0.00410 AC XY: 1832 AN XY: 447000

Gnomad4 AFR exome AF: 0.00157

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00173

Gnomad4 SAS exome AF: 0.00387

Gnomad4 FIN exome AF: 0.00205

Gnomad4 NFE exome AF: 0.00485

Gnomad4 OTH exome AF: 0.00327

GnomAD4 genome AF: 0.0000882 AC: 13 AN: 147390 Hom.: 0 Cov.: 0 AF XY: 0.0000838 AC XY: 6 AN XY: 71592

Gnomad4 AFR AF: 0.000124

Gnomad4 AMR AF: 0.0000676

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000898

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00542 Hom.: 1380

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs11377100; hg19: chr6-110053824;