rs574164748

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

guanidinoacetate methyltransferase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

GAMT 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 (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 VariationId is 205575.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000156.6. 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
	GAMT	NM_000156.6	MANE Select	c.7G>T	p.Ala3Ser	missense	Exon 1 of 6	NP_000147.1	Q14353-1
	GAMT	NM_138924.3		c.7G>T	p.Ala3Ser	missense	Exon 1 of 5	NP_620279.1	Q14353-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAMT	ENST00000252288.8	TSL:1 MANE Select	c.7G>T	p.Ala3Ser	missense	Exon 1 of 6	ENSP00000252288.1	Q14353-1
GAMT	ENST00000902474.1		c.7G>T	p.Ala3Ser	missense	Exon 1 of 6	ENSP00000572533.1
GAMT	ENST00000447102.8	TSL:2	c.7G>T	p.Ala3Ser	missense	Exon 1 of 5	ENSP00000403536.2	Q14353-2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24634

American (AMR)

AF:

0.00

AC:

AN:

15338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18430

East Asian (EAS)

AF:

0.00

AC:

AN:

27170

South Asian (SAS)

AF:

0.0000187

AC:

AN:

53504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3454

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

988406

Other (OTH)

AF:

0.00

AC:

AN:

49386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

5.8

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.32

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.35

M_CAP

Pathogenic

0.89

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.14

PhyloP100

-0.16

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.63

REVEL

Benign

0.22

Sift

Benign

0.43

Sift4G

Benign

0.32

Polyphen

0.0030

Vest4

0.14

MutPred

0.079

Gain of glycosylation at A3 (P = 0.0018)

MVP

0.80

MPC

0.14

ClinPred

0.11

GERP RS

1.3

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.071

gMVP

0.45

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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