rs2296805

chr6-42961020-T-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.206+47T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,456,542 control chromosomes in the GnomAD database, including 264,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (35321 hom., cov: 33)
  • Exomes 𝑓: 0.59 (229499 hom.)
• Consequence: GNMT NM_018960.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.96

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=-0.81).
• BP6: Variant 6-42961020-T-G is Benign according to our data. Variant chr6-42961020-T-G is described in ClinVar as [Benign]. Clinvar id is 1265698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNMT	NM_018960.6	c.206+47T>G		intron_variant		ENST00000372808.4
CNPY3-GNMT	NR_134890.2	n.340-1742T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNMT	ENST00000372808.4	c.206+47T>G		intron_variant		1	NM_018960.6	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100590 AN: 152078 Hom.: 35265 Cov.: 33

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.646

GnomAD3 exomes AF: 0.574 AC: 67666 AN: 117892 Hom.: 20226 AF XY: 0.578 AC XY: 37381 AN XY: 64620

Gnomad AFR exome AF: 0.924

Gnomad AMR exome AF: 0.535

Gnomad ASJ exome AF: 0.520

Gnomad EAS exome AF: 0.343

Gnomad SAS exome AF: 0.649

Gnomad FIN exome AF: 0.512

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.589 AC: 767795 AN: 1304346 Hom.: 229499 Cov.: 21 AF XY: 0.590 AC XY: 379411 AN XY: 642802

Gnomad4 AFR exome AF: 0.925

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.652

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.597

GnomAD4 genome AF: 0.662 AC: 100709 AN: 152196 Hom.: 35321 Cov.: 33 AF XY: 0.655 AC XY: 48733 AN XY: 74420

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.648

Alfa AF: 0.597 Hom.: 8011

Bravo AF: 0.677

Asia WGS AF: 0.544 AC: 1895 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.5
Dann	Benign	0.56

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: rs2296805; hg19: chr6-42928758;