chr15-45378397-G-A

Variant names:

• chr15-45378397-G-A
• rs1052590218
• NM_001482.3:c.57C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001482.3(GATM):​c.57C>T​(p.Tyr19Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000317 in 1,513,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: GATM NM_001482.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.00
• Publications: 0 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, G2P
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 15-45378397-G-A is Benign according to our data. Variant chr15-45378397-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 469140.Status of the report is criteria_provided_single_submitter, 1 stars.

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.57C>T	p.Tyr19Tyr	synonymous	Exon 1 of 9	NP_001473.1
	GATM	NM_001321015.2		c.-318-1578C>T		intron	N/A	NP_001307944.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATM	ENST00000396659.8	TSL:1 MANE Select	c.57C>T	p.Tyr19Tyr	synonymous	Exon 1 of 9	ENSP00000379895.3
	GATM	ENST00000558362.5	TSL:1	n.148C>T		non_coding_transcript_exon	Exon 1 of 8
	GATM	ENST00000887717.1		c.57C>T	p.Tyr19Tyr	synonymous	Exon 1 of 9	ENSP00000557776.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152076 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000888 AC: 1 AN: 112666 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000231

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000316 AC: 43 AN: 1361546 Hom.: 0 Cov.: 30 AF XY: 0.0000298 AC XY: 20 AN XY: 671410

African (AFR) AF: 0.0000349 AC: 1 AN: 28638

American (AMR) AF: 0.0000599 AC: 2 AN: 33412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24280

East Asian (EAS) AF: 0.00 AC: 0 AN: 32946

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4876

European-Non Finnish (NFE) AF: 0.0000337 AC: 36 AN: 1069518

Other (OTH) AF: 0.0000527 AC: 3 AN: 56888

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Arginine:glycine amidinotransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		4.0
PromoterAI		-0.020	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1052590218; hg19: chr15-45670595;