dbSNP rs3800292: GNMT:c.335-191A>G (chr6-42962571-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_018960.6(GNMT):c.335-191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,848 control chromosomes in the GnomAD database, including 1,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1402 hom., cov: 31)

Consequence

GNMT
NM_018960.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0270

Publications

5 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 Gene-Disease associations (from GenCC):

glycine N-methyltransferase deficiency
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

GNMT 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=-0.88).

BP6

Variant 6-42962571-A-G is Benign according to our data. Variant chr6-42962571-A-G is described in ClinVar as Benign. ClinVar VariationId is 1282565.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNMT	NM_018960.6 link	c.335-191A>G		intron_variant	Intron 2 of 5	ENST00000372808.4	NP_061833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNMT	ENST00000372808.4 link	c.335-191A>G		intron_variant	Intron 2 of 5	1	NM_018960.6	ENSP00000361894.3

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15848

AN:

151730

Hom.:

1397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.0419

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0599

Gnomad FIN

AF:

0.0346

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0943

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

GnomAD4 genome

AF:

0.105

AC:

15881

AN:

151848

Hom.:

1402

Cov.:

AF XY:

0.101

AC XY:

7480

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.240

AC:

9920

AN:

41352

American (AMR)

AF:

0.0605

AC:

923

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3470

East Asian (EAS)

AF:

0.0565

AC:

291

AN:

5148

South Asian (SAS)

AF:

0.0591

AC:

284

AN:

4808

European-Finnish (FIN)

AF:

0.0346

AC:

366

AN:

10566

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0541

AC:

3679

AN:

67948

Other (OTH)

AF:

0.0938

AC:

198

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

664

1327

1991

2654

3318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0694

Hom.:

2176

Bravo

AF:

0.114

Asia WGS

AF:

0.0630

AC:

220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

(source)

DANN

Benign

0.63

PhyloP100

-0.027

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over