rs266811

Variant names:

• chr19-1397048-G-C
• rs266811
• NM_000156.6:c.*311C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-1397048-G-C
• chr19-1397048-G-A
• chr19-1397048-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000156.6(GAMT):​c.*311C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 379,452 control chromosomes in the GnomAD database, including 1,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (1006 hom., cov: 33)
  • Exomes 𝑓: 0.020 (251 hom.)
• Consequence: GAMT NM_000156.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.941
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-1397048-G-C is Benign according to our data. Variant chr19-1397048-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 328343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

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.*311C>G		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.*311C>G		3_prime_UTR	Exon 6 of 6	ENSP00000252288.1	Q14353-1
	GAMT	ENST00000902474.1		c.*311C>G		downstream_gene	N/A	ENSP00000572533.1
	GAMT	ENST00000902472.1		c.*311C>G		downstream_gene	N/A	ENSP00000572531.1

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10564 AN: 152072 Hom.: 1007 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00901

Gnomad OTH AF: 0.0584

GnomAD4 exome AF: 0.0198 AC: 4496 AN: 227262 Hom.: 251 Cov.: 0 AF XY: 0.0191 AC XY: 2263 AN XY: 118776

African (AFR) AF: 0.225 AC: 1700 AN: 7546

American (AMR) AF: 0.0338 AC: 387 AN: 11436

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 202 AN: 7204

East Asian (EAS) AF: 0.000140 AC: 2 AN: 14324

South Asian (SAS) AF: 0.0173 AC: 454 AN: 26206

European-Finnish (FIN) AF: 0.00221 AC: 28 AN: 12658

Middle Eastern (MID) AF: 0.0559 AC: 57 AN: 1020

European-Non Finnish (NFE) AF: 0.00959 AC: 1281 AN: 133560

Other (OTH) AF: 0.0289 AC: 385 AN: 13308

GnomAD4 genome AF: 0.0695 AC: 10582 AN: 152190 Hom.: 1006 Cov.: 33 AF XY: 0.0671 AC XY: 4992 AN XY: 74416

African (AFR) AF: 0.216 AC: 8976 AN: 41468

American (AMR) AF: 0.0422 AC: 645 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10632

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00900 AC: 612 AN: 67996

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0118 Hom.: 21

Bravo AF: 0.0803

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Deficiency of guanidinoacetate methyltransferase (1)
-	-	1	Leigh syndrome (1)
-	-	1	Mitochondrial complex I deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.78
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs266811; hg19: chr19-1397047;