chr6-42961014-G-A

Position:

• chr6-42961014-G-A

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+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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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 6-42961014-G-A is Benign according to our data. Variant chr6-42961014-G-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNMT	NM_018960.6	c.206+41G>A		intron_variant		ENST00000372808.4	NP_061833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNMT	ENST00000372808.4	c.206+41G>A		intron_variant		1	NM_018960.6	ENSP00000361894.3

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6311 AN: 152214 Hom.: 465 Cov.: 34

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

GnomAD3 exomes AF: 0.00906 AC: 1102 AN: 121666 Hom.: 71 AF XY: 0.00718 AC XY: 479 AN XY: 66738

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 SAS exome AF: 0.000242

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.: 23 AF XY: 0.00358 AC XY: 2355 AN XY: 657672

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.00867

Gnomad4 ASJ exome AF: 0.000124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000312

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.00875

GnomAD4 genome AF: 0.0415 AC: 6319 AN: 152332 Hom.: 465 Cov.: 34 AF XY: 0.0405 AC XY: 3014 AN XY: 74500

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.00595 Hom.: 6

Bravo AF: 0.0483

Asia WGS AF: 0.00837 AC: 30 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.79

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: rs5031030; hg19: chr6-42928752;