19-1397083-G-T

Variant names:

• chr19-1397083-G-T
• rs266810
• NM_000156.6:c.*276C>A

Variant summary

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

The NM_000156.6(GAMT):​c.*276C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 316,816 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: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: GAMT NM_000156.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 0 publications found

Genes affected

GAMT (HGNC:4136): (guanidinoacetate N-methyltransferase) The protein encoded by this gene is a methyltransferase that converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor. Defects in this gene have been implicated in neurologic syndromes and muscular hypotonia, probably due to creatine deficiency and accumulation of guanidinoacetate in the brain of affected individuals. Two transcript variants encoding different isoforms have been described for this gene. Pseudogenes of this gene are found on chromosomes 2 and 13. [provided by RefSeq, Feb 2012]

GAMT Gene-Disease associations (from GenCC):

• guanidinoacetate methyltransferase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000156.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAMT	NM_000156.6	MANE Select	c.*276C>A		3_prime_UTR	Exon 6 of 6	NP_000147.1	Q14353-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAMT	ENST00000252288.8	TSL:1 MANE Select	c.*276C>A		3_prime_UTR	Exon 6 of 6	ENSP00000252288.1	Q14353-1
	GAMT	ENST00000902474.1		c.*276C>A		downstream_gene	N/A	ENSP00000572533.1
	GAMT	ENST00000902472.1		c.*276C>A		downstream_gene	N/A	ENSP00000572531.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000631 AC: 2 AN: 316816 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 164774

African (AFR) AF: 0.00 AC: 0 AN: 9836

American (AMR) AF: 0.00 AC: 0 AN: 14624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10060

East Asian (EAS) AF: 0.00 AC: 0 AN: 21858

South Asian (SAS) AF: 0.00 AC: 0 AN: 32144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1404

European-Non Finnish (NFE) AF: 0.0000106 AC: 2 AN: 188400

Other (OTH) AF: 0.00 AC: 0 AN: 18678

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.51
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs266810; hg19: chr19-1397082;