chr15-45361196-C-T

Position:

• chr15-45361196-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001482.3(GATM):​c.*913G>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 0.0857 in 152,070 control chromosomes in the GnomAD database, including 724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (724 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GATM NM_001482.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.581

Genes affected

GATM (HGNC:4175): (glycine amidinotransferase) This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine. Mutations in this gene cause arginine:glycine amidinotransferase deficiency, an inborn error of creatine synthesis characterized by cognitive disability, language impairment, and behavioral disorders. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-45361196-C-T is Benign according to our data. Variant chr15-45361196-C-T is described in ClinVar as [Benign]. Clinvar id is 316201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATM	NM_001482.3	c.*913G>A		3_prime_UTR_variant	9/9	ENST00000396659.8	NP_001473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATM	ENST00000396659.8	c.*913G>A		3_prime_UTR_variant	9/9	1	NM_001482.3	ENSP00000379895	P1
GATM	ENST00000558362.5	n.3841G>A		non_coding_transcript_exon_variant	8/8	1
GATM	ENST00000675323.1	c.*2687G>A		3_prime_UTR_variant	8/8			ENSP00000502445
GATM	ENST00000676090.1	c.*2916G>A		3_prime_UTR_variant, NMD_transcript_variant	10/10			ENSP00000501630

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13033 AN: 151952 Hom.: 723 Cov.: 33

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0857 AC: 13034 AN: 152070 Hom.: 724 Cov.: 33 AF XY: 0.0855 AC XY: 6357 AN XY: 74336

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.109

Alfa AF: 0.107 Hom.: 322

Bravo AF: 0.0868

Asia WGS AF: 0.0320 AC: 111 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Arginine:glycine amidinotransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.51

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: rs17618637; hg19: chr15-45653394;