6-42960779-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_018960.6(GNMT):c.12C>T(p.Ser4Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,542,254 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

GNMT
NM_018960.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.773

Publications

0 publications found

Variant links:

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]

GNMT links:

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

PEX6 links:

CNPY3-GNMT (HGNC:):

CNPY3-GNMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 6-42960779-C-T is Benign according to our data. Variant chr6-42960779-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168628.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.773 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNMT	NM_018960.6	MANE Select	c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 6	NP_061833.1	Q14749
GNMT	NM_001318865.2		c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 6	NP_001305794.1	A0A0S2Z5F2
CNPY3-GNMT	NM_001318857.2		c.152-1983C>T		intron	N/A	NP_001305786.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNMT	ENST00000372808.4	TSL:1 MANE Select	c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 6	ENSP00000361894.3	Q14749
GNMT	ENST00000858688.1		c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 6	ENSP00000528747.1
GNMT	ENST00000858686.1		c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 6	ENSP00000528745.1

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

226

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000375

AC:

AN:

149264

AF XY:

0.000336

show subpopulations

Gnomad AFR exome

AF:

0.00517

Gnomad AMR exome

AF:

0.000317

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000506

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000151

AC:

210

AN:

1389908

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

684648

show subpopulations

African (AFR)

AF:

0.00502

AC:

159

AN:

31644

American (AMR)

AF:

0.000387

AC:

AN:

36140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24398

East Asian (EAS)

AF:

0.00

AC:

AN:

36230

South Asian (SAS)

AF:

0.0000512

AC:

AN:

78072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43596

Middle Eastern (MID)

AF:

0.000371

AC:

AN:

5390

European-Non Finnish (NFE)

AF:

0.0000130

AC:

AN:

1076796

Other (OTH)

AF:

0.000295

AC:

AN:

57642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00150

AC:

228

AN:

152346

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00517

AC:

215

AN:

41578

American (AMR)

AF:

0.000588

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.00170

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

GNMT-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.77

PromoterAI

0.088

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over