Genetic Variant GATM:p.Ala14Ala (chr15-45378412-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001482.3(GATM):c.42C>T(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A14A) has been classified as Likely benign. The gene GATM is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GATM
NM_001482.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.718

Publications

0 publications found

Variant links:

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

GATM links:

ENSG00000275672 (HGNC:):

ENSG00000275672 links:

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ACMG classification

Specifications for GATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP7

Synonymous conserved (PhyloP=0.718 with no splicing effect.

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.42C>T	p.Ala14Ala	synonymous	Exon 1 of 9	NP_001473.1	P50440-1
	GATM	NM_001321015.2		c.-318-1593C>T		intron	N/A	NP_001307944.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATM	ENST00000396659.8	TSL:1 MANE Select	c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 9	ENSP00000379895.3	P50440-1
GATM	ENST00000558362.5	TSL:1	n.133C>T		non_coding_transcript_exon	Exon 1 of 8
GATM	ENST00000887717.1		c.42C>T	p.Ala14Ala	synonymous	Exon 1 of 9	ENSP00000557776.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1352610

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666658

African (AFR)

AF:

0.00

AC:

AN:

27850

American (AMR)

AF:

0.00

AC:

AN:

31922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23934

East Asian (EAS)

AF:

0.00

AC:

AN:

31978

South Asian (SAS)

AF:

0.00

AC:

AN:

75860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4830

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065614

Other (OTH)

AF:

0.00

AC:

AN:

56402

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.72

PromoterAI

-0.024

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over