rs17618637

Variant names:

• chr15-45361196-C-T
• rs17618637
• NM_001482.3:c.*913G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

GATM Gene-Disease associations (from GenCC):

• AGAT deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• Fanconi renotubular syndrome 1

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• primary Fanconi syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001482.3. 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
	GATM	NM_001482.3	MANE Select	c.*913G>A		3_prime_UTR	Exon 9 of 9	NP_001473.1	P50440-1
	GATM	NM_001321015.2		c.*913G>A		3_prime_UTR	Exon 12 of 12	NP_001307944.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATM	ENST00000396659.8	TSL:1 MANE Select	c.*913G>A		3_prime_UTR	Exon 9 of 9	ENSP00000379895.3	P50440-1
	GATM	ENST00000558362.5	TSL:1	n.3841G>A		non_coding_transcript_exon	Exon 8 of 8
	GATM	ENST00000887717.1		c.*913G>A		3_prime_UTR	Exon 9 of 9	ENSP00000557776.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0209 AC: 867 AN: 41478

American (AMR) AF: 0.130 AC: 1977 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1132 AN: 10562

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7956 AN: 67978

Other (OTH) AF: 0.109 AC: 231 AN: 2114

Alfa AF: 0.106 Hom.: 348

Bravo AF: 0.0868

Asia WGS AF: 0.0320 AC: 111 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Arginine:glycine amidinotransferase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.51
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17618637; hg19: chr15-45653394;