Variant 19-1401470-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_ModerateBP6_Moderate

The NM_000156.6(GAMT):c.7G>T(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000827 in 1,209,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

GAMT
NM_000156.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.157

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a chain Guanidinoacetate N-methyltransferase (size 234) in uniprot entity GAMT_HUMAN there are 37 pathogenic changes around while only 8 benign (82%) in NM_000156.6

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14780992).

BP6

Variant 19-1401470-C-A is Benign according to our data. Variant chr19-1401470-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 205575.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAMT	NM_000156.6 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/6	ENST00000252288.8	NP_000147.1
GAMT	NM_138924.3 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/5		NP_620279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAMT	ENST00000252288.8 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/6	1	NM_000156.6	ENSP00000252288	P1	Q14353-1
GAMT	ENST00000447102.8 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/5	2		ENSP00000403536		Q14353-2
GAMT	ENST00000640762.1 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/6	5		ENSP00000492031

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.27e-7

AC:

AN:

1209714

Hom.:

Cov.:

AF XY:

0.00000170

AC XY:

AN XY:

588214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

5.8

DANN

Benign

0.95

DEOGEN2

Benign

0.32

T;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.35

T;T;T

M_CAP

Pathogenic

0.89

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.14

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.63

N;.;N

REVEL

Benign

0.22

Sift

Benign

0.43

T;.;T

Sift4G

Benign

0.32

T;.;T

Polyphen

0.0030

B;.;.

Vest4

0.14

MutPred

0.079

Gain of glycosylation at A3 (P = 0.0018);Gain of glycosylation at A3 (P = 0.0018);Gain of glycosylation at A3 (P = 0.0018);

MVP

0.80

MPC

0.14

ClinPred

0.11

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.071

gMVP

0.45

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