6-109732621-GT-GTTTT

Position:

• chr6-109732621-GT-GTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PVS1_Moderate BP6_Moderate

The NM_014845.6(FIG4):​c.447-5_447-3dupTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: FIG4 NM_014845.6 splice_acceptor, 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]

FIG4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.01835536 fraction of the gene. Cryptic splice site detected, with MaxEntScore 13, offset of 0 (no position change), new splice context is: tgttttttttttttttttAGgta. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BP6: Variant 6-109732621-G-GTTT is Benign according to our data. Variant chr6-109732621-G-GTTT is described in ClinVar as [Benign]. Clinvar id is 2060022.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIG4	NM_014845.6	c.447-5_447-3dupTTT		splice_acceptor_variant, intron_variant		ENST00000230124.8	NP_055660.1
FIG4	XM_011536281.4	c.384-5_384-3dupTTT		splice_acceptor_variant, intron_variant			XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8	c.447-5_447-3dupTTT		splice_acceptor_variant, intron_variant		1	NM_014845.6	ENSP00000230124.4

Frequencies

GnomAD3 genomes AF: 0.0000611 AC: 9 AN: 147350 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00147 AC: 1269 AN: 860588 Hom.: 0 Cov.: 17 AF XY: 0.00127 AC XY: 567 AN XY: 446810

Gnomad4 AFR exome AF: 0.00350

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.00108

Gnomad4 EAS exome AF: 0.000328

Gnomad4 SAS exome AF: 0.000878

Gnomad4 FIN exome AF: 0.000451

Gnomad4 NFE exome AF: 0.00164

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.0000678 AC: 10 AN: 147398 Hom.: 0 Cov.: 0 AF XY: 0.0000698 AC XY: 5 AN XY: 71592

Gnomad4 AFR AF: 0.000223

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000110

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

Labcorp Genetics (formerly Invitae), Labcorp

Nov 24, 2023

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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;