rs58057801

Variant names:

• chr6-42961623-G-A
• rs58057801
• NM_018960.6:c.207-589G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-42961623-G-A
• chr6-42961623-G-C

Variant summary

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

The NM_018960.6(GNMT):​c.207-589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 145,220 control chromosomes in the GnomAD database, including 129 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 0.024 (129 hom., cov: 28)
• Consequence: GNMT NM_018960.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645
• Publications: 0 publications found

Genes affected

GNMT (HGNC:4415): (glycine N-methyltransferase) The protein encoded by this gene is an enzyme that catalyzes the conversion of S-adenosyl-L-methionine (along with glycine) to S-adenosyl-L-homocysteine and sarcosine. This protein is found in the cytoplasm and acts as a homotetramer. Defects in this gene are a cause of GNMT deficiency (hypermethioninemia). Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between the upstream CNPY3 (canopy FGF signaling regulator 3) gene and this gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PEX6 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 4A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health
• peroxisome biogenesis disorder 4B

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Heimler syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: G2P
• autosomal recessive cerebellar ataxia-blindness-deafness syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CNPY3-GNMT (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018960.6. 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
	GNMT	NM_018960.6	MANE Select	c.207-589G>A		intron	N/A	NP_061833.1	Q14749
	GNMT	NM_001318865.2		c.207-589G>A		intron	N/A	NP_001305794.1	A0A0S2Z5F2
	CNPY3-GNMT	NM_001318857.2		c.152-1139G>A		intron	N/A	NP_001305786.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNMT	ENST00000372808.4	TSL:1 MANE Select	c.207-589G>A		intron	N/A	ENSP00000361894.3	Q14749
	PEX6	ENST00000970120.1		c.*861C>T		3_prime_UTR	Exon 18 of 18	ENSP00000640179.1
	PEX6	ENST00000858651.1		c.*861C>T		3_prime_UTR	Exon 18 of 18	ENSP00000528710.1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3423 AN: 145112 Hom.: 129 Cov.: 28

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000219

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.000164

Gnomad OTH AF: 0.0173

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

GnomAD4 genome AF: 0.0236 AC: 3425 AN: 145220 Hom.: 129 Cov.: 28 AF XY: 0.0230 AC XY: 1607 AN XY: 69916

African (AFR) AF: 0.0817 AC: 3242 AN: 39684

American (AMR) AF: 0.0102 AC: 136 AN: 13328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 4760

South Asian (SAS) AF: 0.000220 AC: 1 AN: 4548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9022

Middle Eastern (MID) AF: 0.00379 AC: 1 AN: 264

European-Non Finnish (NFE) AF: 0.000164 AC: 11 AN: 67266

Other (OTH) AF: 0.0172 AC: 34 AN: 1982

Alfa AF: 0.00415 Hom.: 2

Bravo AF: 0.0271

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		-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

Other links and lift over

dbSNP: rs58057801; hg19: chr6-42929361;