NM_014845.6:c.66+2178C>T

Variant names:

• chr6-109693679-C-T
• rs829811
• NM_014845.6:c.66+2178C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014845.6(FIG4):​c.66+2178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,074 control chromosomes in the GnomAD database, including 47,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47486 hom., cov: 30)
• Consequence: FIG4 NM_014845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• Charcot-Marie-Tooth disease type 4J

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine
• Yunis-Varon syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• amyotrophic lateral sclerosis type 11

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• bilateral parasagittal parieto-occipital polymicrogyria

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIG4	NM_014845.6	c.66+2178C>T		intron_variant	Intron 1 of 22	ENST00000230124.8	NP_055660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8	c.66+2178C>T		intron_variant	Intron 1 of 22	1	NM_014845.6	ENSP00000230124.4

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119875 AN: 151956 Hom.: 47440 Cov.: 30

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.775

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.789 AC: 119985 AN: 152074 Hom.: 47486 Cov.: 30 AF XY: 0.786 AC XY: 58415 AN XY: 74310

African (AFR) AF: 0.865 AC: 35870 AN: 41480

American (AMR) AF: 0.764 AC: 11670 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2657 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3553 AN: 5166

South Asian (SAS) AF: 0.665 AC: 3194 AN: 4806

European-Finnish (FIN) AF: 0.783 AC: 8281 AN: 10576

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52266 AN: 67988

Other (OTH) AF: 0.774 AC: 1635 AN: 2112

Alfa AF: 0.758 Hom.: 11565

Bravo AF: 0.792

Asia WGS AF: 0.696 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.094
DANN	Benign	0.34
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs829811; hg19: chr6-110014882;