rs7760250

chr6-42962101-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.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

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=-0.83).
• BP6: Variant 6-42962101-G-A is Benign according to our data. Variant chr6-42962101-G-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
GNMT	NM_018960.6	c.207-111G>A		intron_variant		ENST00000372808.4
CNPY3-GNMT	NR_134890.2	n.340-661G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNMT	ENST00000372808.4	c.207-111G>A		intron_variant		1	NM_018960.6	P1

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

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.514

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

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.546

Alfa AF: 0.553 Hom.: 2964

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

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	-0.83
Cadd	Benign	3.8
Dann	Benign	0.67

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: rs7760250; hg19: chr6-42929839; COSMIC: COSV55106437; COSMIC: COSV55106437;