Variant 3-49416844-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000481.4(AMT):c.*696C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 454,902 control chromosomes in the GnomAD database, including 20,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6707 hom., cov: 31)

Exomes 𝑓: 0.28 ( 13673 hom. )

Consequence

AMT
NM_000481.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

AMT (HGNC:473): (aminomethyltransferase) This gene encodes one of four critical components of the glycine cleavage system. Mutations in this gene have been associated with glycine encephalopathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

AMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-49416844-G-A is Benign according to our data. Variant chr3-49416844-G-A is described in ClinVar as [Benign]. Clinvar id is 346021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMT	NM_000481.4 linkuse as main transcript	c.*696C>T		3_prime_UTR_variant	9/9	ENST00000273588.9	NP_000472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMT	ENST00000273588.9 linkuse as main transcript	c.*696C>T		3_prime_UTR_variant	9/9	1	NM_000481.4	ENSP00000273588	P1	P48728-1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43250

AN:

151730

Hom.:

6702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.0585

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.264

AC:

34458

AN:

130456

Hom.:

5493

AF XY:

0.266

AC XY:

18956

AN XY:

71208

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.0528

Gnomad SAS exome

AF:

0.240

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.285

AC:

86290

AN:

303054

Hom.:

13673

Cov.:

AF XY:

0.282

AC XY:

48638

AN XY:

172610

show subpopulations

Gnomad4 AFR exome

AF:

0.246

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.458

Gnomad4 EAS exome

AF:

0.0548

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.456

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.285

AC:

43272

AN:

151848

Hom.:

6707

Cov.:

AF XY:

0.288

AC XY:

21360

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.0589

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.305

Hom.:

7692

Bravo

AF:

0.263

Asia WGS

AF:

0.144

AC:

507

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Non-ketotic hyperglycinemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.5

DANN

Benign

0.54

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