chr15-45362117-A-G

Position:

• chr15-45362117-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001482.3(GATM):​c.1264T>C​(p.Leu422=) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATM NM_001482.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.87

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 15-45362117-A-G is Benign according to our data. Variant chr15-45362117-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1545357.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATM	NM_001482.3	c.1264T>C	p.Leu422=	synonymous_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.1264T>C	p.Leu422=	synonymous_variant	9/9	1	NM_001482.3	ENSP00000379895	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Arginine:glycine amidinotransferase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 16, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.4
DANN	Benign	0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45654315;