chr6-42962101-G-A

Variant names:

• chr6-42962101-G-A
• rs7760250
• NM_018960.6:c.207-111G>A

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.207-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,237,874 control chromosomes in the GnomAD database, including 174,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24780 hom., cov: 31)
  • Exomes 𝑓: 0.52 (149326 hom.)
• Consequence: GNMT NM_018960.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0140
• Publications: 10 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=-0.83).
• BP6: Variant 6-42962101-G-A is Benign according to our data. Variant chr6-42962101-G-A is described in ClinVar as Benign. ClinVar VariationId is 1230082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNMT	NM_018960.6	c.207-111G>A		intron_variant	Intron 1 of 5	ENST00000372808.4	NP_061833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNMT	ENST00000372808.4	c.207-111G>A		intron_variant	Intron 1 of 5	1	NM_018960.6	ENSP00000361894.3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84535 AN: 151790 Hom.: 24743 Cov.: 31

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.516 AC: 560608 AN: 1085966 Hom.: 149326 AF XY: 0.518 AC XY: 287254 AN XY: 554710

African (AFR) AF: 0.730 AC: 19044 AN: 26098

American (AMR) AF: 0.334 AC: 13694 AN: 41046

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 10956 AN: 23498

East Asian (EAS) AF: 0.206 AC: 7627 AN: 36974

South Asian (SAS) AF: 0.521 AC: 39875 AN: 76604

European-Finnish (FIN) AF: 0.454 AC: 21311 AN: 46992

Middle Eastern (MID) AF: 0.569 AC: 2574 AN: 4522

European-Non Finnish (NFE) AF: 0.538 AC: 420899 AN: 782296

Other (OTH) AF: 0.514 AC: 24628 AN: 47936

GnomAD4 genome AF: 0.557 AC: 84624 AN: 151908 Hom.: 24780 Cov.: 31 AF XY: 0.548 AC XY: 40692 AN XY: 74256

African (AFR) AF: 0.727 AC: 30132 AN: 41450

American (AMR) AF: 0.418 AC: 6375 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3468

East Asian (EAS) AF: 0.182 AC: 939 AN: 5146

South Asian (SAS) AF: 0.491 AC: 2370 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4911 AN: 10552

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36376 AN: 67922

Other (OTH) AF: 0.546 AC: 1153 AN: 2110

Alfa AF: 0.560 Hom.: 3171

Bravo AF: 0.561

Asia WGS AF: 0.352 AC: 1228 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		0.014
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: rs7760250; hg19: chr6-42929839; COSMIC: COSV55106437; COSMIC: COSV55106437;