6-109798928-T-G

Variant names:

• chr6-109798928-T-G
• rs4330563
• NM_014845.6:c.2546+2077T>G

Variant summary

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

The NM_014845.6(FIG4):​c.2546+2077T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,886 control chromosomes in the GnomAD database, including 30,712 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 0.61 (30712 hom., cov: 31)
• Consequence: FIG4 NM_014845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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.2546+2077T>G		intron_variant	Intron 22 of 22	ENST00000230124.8	NP_055660.1
FIG4	XM_011536281.4	c.2483+2077T>G		intron_variant	Intron 22 of 22		XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8	c.2546+2077T>G		intron_variant	Intron 22 of 22	1	NM_014845.6	ENSP00000230124.4

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92578 AN: 151768 Hom.: 30652 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.610 AC: 92700 AN: 151886 Hom.: 30712 Cov.: 31 AF XY: 0.614 AC XY: 45580 AN XY: 74242

African (AFR) AF: 0.865 AC: 35844 AN: 41460

American (AMR) AF: 0.596 AC: 9097 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2138 AN: 3470

East Asian (EAS) AF: 0.840 AC: 4344 AN: 5174

South Asian (SAS) AF: 0.694 AC: 3339 AN: 4810

European-Finnish (FIN) AF: 0.493 AC: 5175 AN: 10500

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30866 AN: 67900

Other (OTH) AF: 0.610 AC: 1283 AN: 2102

Alfa AF: 0.545 Hom.: 3966

Bravo AF: 0.628

Asia WGS AF: 0.761 AC: 2633 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.9
DANN	Benign	0.65
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

Publications

LitVar

Other links and lift over

dbSNP: rs4330563; hg19: chr6-110120131;