6-42962571-A-G

Variant names:

• chr6-42962571-A-G
• rs3800292
• NM_018960.6:c.335-191A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270
• Publications: 5 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]

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

CNPY3-GNMT (HGNC:):

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNMT	NM_018960.6	MANE Select	c.335-191A>G		intron	N/A	NP_061833.1
	GNMT	NM_001318865.2		c.335-191A>G		intron	N/A	NP_001305794.1
	CNPY3-GNMT	NM_001318857.2		c.152-191A>G		intron	N/A	NP_001305786.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNMT	ENST00000372808.4	TSL:1 MANE Select	c.335-191A>G		intron	N/A	ENSP00000361894.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15848 AN: 151730 Hom.: 1397 Cov.: 31

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.: 31 AF XY: 0.101 AC XY: 7480 AN XY: 74206

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: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0541 AC: 3679 AN: 67948

Other (OTH) AF: 0.0938 AC: 198 AN: 2110

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.027
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: rs3800292; hg19: chr6-42930309; COSMIC: COSV107302315; COSMIC: COSV107302315;