rs5031030

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018960.6(GNMT):c.206+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00805 in 1,486,288 control chromosomes in the GnomAD database, including 817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 465 hom., cov: 34)

Exomes 𝑓: 0.0042 ( 352 hom. )

Consequence

GNMT
NM_018960.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.29

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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-42961014-G-A is Benign according to our data. Variant chr6-42961014-G-A is described in ClinVar as Benign. ClinVar VariationId is 1238861.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNMT	NM_018960.6	MANE Select	c.206+41G>A	intron	N/A	NP_061833.1	Q14749
GNMT	NM_001318865.2		c.206+41G>A	intron	N/A	NP_001305794.1	A0A0S2Z5F2
CNPY3-GNMT	NM_001318857.2		c.152-1748G>A	intron	N/A	NP_001305786.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNMT	ENST00000372808.4	TSL:1 MANE Select	c.206+41G>A	intron	N/A	ENSP00000361894.3	Q14749
PEX6	ENST00000970120.1		c.*1470C>T	3_prime_UTR	Exon 18 of 18	ENSP00000640179.1
GNMT	ENST00000858688.1		c.206+41G>A	intron	N/A	ENSP00000528747.1

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6311

AN:

152214

Hom.:

465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.00906

AC:

1102

AN:

121666

AF XY:

0.00718

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.00652

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000445

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00424

AC:

5653

AN:

1333956

Hom.:

352

Cov.:

AF XY:

0.00358

AC XY:

2355

AN XY:

657672

show subpopulations

African (AFR)

AF:

0.151

AC:

4578

AN:

30298

American (AMR)

AF:

0.00867

AC:

302

AN:

34830

Ashkenazi Jewish (ASJ)

AF:

0.000124

AC:

AN:

24218

East Asian (EAS)

AF:

0.00

AC:

AN:

35302

South Asian (SAS)

AF:

0.000312

AC:

AN:

77006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34052

Middle Eastern (MID)

AF:

0.00608

AC:

AN:

4276

European-Non Finnish (NFE)

AF:

0.000223

AC:

232

AN:

1038186

Other (OTH)

AF:

0.00875

AC:

488

AN:

55788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

264

527

791

1054

1318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<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:

0.0415

AC:

6319

AN:

152332

Hom.:

465

Cov.:

AF XY:

0.0405

AC XY:

3014

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.144

AC:

5964

AN:

41560

American (AMR)

AF:

0.0157

AC:

240

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68034

Other (OTH)

AF:

0.0341

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

278

557

835

1114

1392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.00926

Hom.:

Bravo

AF:

0.0483

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

(source)

DANN

Benign

0.79

PhyloP100

-2.3

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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