Variant chr19-1397357-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000252288(GAMT):c.*2C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,609,686 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

GAMT
ENST00000252288 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

GAMT (HGNC:4136): (guanidinoacetate N-methyltransferase) The protein encoded by this gene is a methyltransferase that converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor. Defects in this gene have been implicated in neurologic syndromes and muscular hypotonia, probably due to creatine deficiency and accumulation of guanidinoacetate in the brain of affected individuals. Two transcript variants encoding different isoforms have been described for this gene. Pseudogenes of this gene are found on chromosomes 2 and 13. [provided by RefSeq, Feb 2012]

GAMT links:

GAMT (HGNC:):

GAMT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 19-1397357-G-C is Benign according to our data. Variant chr19-1397357-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 377910.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAMT	NM_000156.6 linkuse as main transcript	c.*2C>G		3_prime_UTR_variant	6/6	ENST00000252288.8	NP_000147.1	Q14353-1V9HWB2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GAMT	ENST00000252288 linkuse as main transcript	c.*2C>G	3_prime_UTR_variant	6/6	1	NM_000156.6	ENSP00000252288.1	Q14353-1
GAMT	ENST00000640762 linkuse as main transcript	c.*2C>G	3_prime_UTR_variant	6/6	5		ENSP00000492031.1	A0A1W2PR36
GAMT	ENST00000640164.1 linkuse as main transcript	n.*26C>G	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.0757

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000745

AC:

AN:

241760

Hom.:

AF XY:

0.0000759

AC XY:

AN XY:

131710

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000526

Gnomad NFE exome

AF:

0.000156

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1457462

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

725094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000393

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000572

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.000778

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over