rs10948059

Variant names:

• chr6-42960723-C-G
• rs10948059
• NM_001318857.2:c.152-2039C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-42960723-C-G
• chr6-42960723-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318857.2(CNPY3-GNMT):​c.152-2039C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CNPY3-GNMT NM_001318857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 45 publications found

Genes affected

CNPY3-GNMT (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNMT	NM_018960.6	c.-45C>G		upstream_gene_variant		ENST00000372808.4	NP_061833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNMT	ENST00000372808.4	c.-45C>G		upstream_gene_variant		1	NM_018960.6	ENSP00000361894.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1310362 Hom.: 0 Cov.: 27 AF XY: 0.00000157 AC XY: 1 AN XY: 637264

African (AFR) AF: 0.00 AC: 0 AN: 28836

American (AMR) AF: 0.00 AC: 0 AN: 29436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20734

East Asian (EAS) AF: 0.00 AC: 0 AN: 34000

South Asian (SAS) AF: 0.00 AC: 0 AN: 67932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4386

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1033910

Other (OTH) AF: 0.0000183 AC: 1 AN: 54568

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 8007

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.38
PhyloP100		-0.33
PromoterAI		-0.076	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10948059; hg19: chr6-42928461;