rs1408966015

Variant names:

• chr6-109691284-C-A
• rs1408966015
• ENST00000674744.1:c.-152C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-109691284-C-A
• chr6-109691284-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000674744.1(FIG4):​c.-152C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 690,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: FIG4 ENST00000674744.1 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.760
• Publications: 0 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]

AK9 (HGNC:33814): (adenylate kinase 9) The protein encoded by this gene catalyzes the interconversion of nucleosides, possessing both nucleoside monophosphate and diphosphate kinase activities. The encoded protein uses these interconversions to maintain nucleoside homeostasis. [provided by RefSeq, Jul 2016]

AK9 Gene-Disease associations (from GenCC):

• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674744.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK9	NM_001145128.3	MANE Select	c.-149G>T		upstream_gene	N/A	NP_001138600.2	Q5TCS8-4
	FIG4	NM_014845.6	MANE Select	c.-152C>A		upstream_gene	N/A	NP_055660.1	Q92562
	AK9	NM_001329603.2		c.-825G>T		upstream_gene	N/A	NP_001316532.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIG4	ENST00000674744.1		c.-152C>A		5_prime_UTR	Exon 1 of 23	ENSP00000501661.1	A0A6Q8PF62
	FIG4	ENST00000675726.1		c.-152C>A		5_prime_UTR	Exon 1 of 22	ENSP00000502452.1	A0A6Q8PGY7
	FIG4	ENST00000676442.1		c.-152C>A		5_prime_UTR	Exon 1 of 22	ENSP00000502595.1	A0A6Q8PHC7

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 151064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000591

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000204 AC: 11 AN: 539078 Hom.: 0 Cov.: 6 AF XY: 0.0000175 AC XY: 5 AN XY: 286404

African (AFR) AF: 0.00 AC: 0 AN: 15214

American (AMR) AF: 0.00 AC: 0 AN: 30154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17772

East Asian (EAS) AF: 0.00 AC: 0 AN: 31218

South Asian (SAS) AF: 0.00 AC: 0 AN: 58478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3918

European-Non Finnish (NFE) AF: 0.0000347 AC: 11 AN: 317164

Other (OTH) AF: 0.00 AC: 0 AN: 29236

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 151064 Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2 AN XY: 73750

African (AFR) AF: 0.00 AC: 0 AN: 41040

American (AMR) AF: 0.00 AC: 0 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000591 AC: 4 AN: 67708

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Amyotrophic lateral sclerosis type 11 (1)
-	1	-	Charcot-Marie-Tooth disease type 4J (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.80
PhyloP100		0.76
PromoterAI		-0.32	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1408966015; hg19: chr6-110012487;