rs3800292

Positions:

• chr6-42962571-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

CNPY3-GNMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
GNMT	NM_018960.6	c.335-191A>G		intron_variant		ENST00000372808.4
CNPY3-GNMT	NR_134890.2	n.340-191A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNMT	ENST00000372808.4	c.335-191A>G		intron_variant		1	NM_018960.6	P1

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

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.0605

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.0565

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.0346

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.0600 Hom.: 627

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs3800292; hg19: chr6-42930309;