dbSNP rs3809472: GATM:n.208C>T (chr15-45402120-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000458245.5(GATM):n.208C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GATM
ENST00000458245.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.520

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 links:

AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

AFG2B Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive 119
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder with hearing loss and spasticity
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

AFG2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG2B	NM_024063.3 link	c.-310G>A		upstream_gene_variant		ENST00000305560.11	NP_076968.2	Q9BVQ7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATM	ENST00000458245.5 link	n.208C>T	non_coding_transcript_exon_variant	Exon 1 of 5	1
GATM	ENST00000561148.5 link	c.-711C>T	5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000453860.1	H0YN43
AFG2B	ENST00000305560.11 link	c.-310G>A	upstream_gene_variant		1	NM_024063.3	ENSP00000305494.6	Q9BVQ7-1
AFG2B	ENST00000559860.2 link	n.-250G>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

243932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

126430

African (AFR)

AF:

0.00

AC:

AN:

5678

American (AMR)

AF:

0.00

AC:

AN:

5176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8232

East Asian (EAS)

AF:

0.00

AC:

AN:

13666

South Asian (SAS)

AF:

0.00

AC:

AN:

21772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

153980

Other (OTH)

AF:

0.00

AC:

AN:

15636

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41516

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.6

(source)

DANN

Benign

0.79

PhyloP100

-0.52

PromoterAI

0.029

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over