chr3-49421681-A-C

Position:

• chr3-49421681-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000481.4(AMT):​c.259-109T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 981,850 control chromosomes in the GnomAD database, including 118,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15845 hom., cov: 32)
  • Exomes 𝑓: 0.47 (102447 hom.)
• Consequence: AMT NM_000481.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-49421681-A-C is Benign according to our data. Variant chr3-49421681-A-C is described in ClinVar as [Benign]. Clinvar id is 1185268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49421681-A-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMT	NM_000481.4	c.259-109T>G		intron_variant		ENST00000273588.9	NP_000472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMT	ENST00000273588.9	c.259-109T>G		intron_variant		1	NM_000481.4	ENSP00000273588	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66447 AN: 151868 Hom.: 15835 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.475 AC: 393904 AN: 829864 Hom.: 102447 Cov.: 11 AF XY: 0.482 AC XY: 210521 AN XY: 436640

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.699

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.437 AC: 66489 AN: 151986 Hom.: 15845 Cov.: 32 AF XY: 0.443 AC XY: 32946 AN XY: 74298

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.440

Alfa AF: 0.429 Hom.: 2288

Bravo AF: 0.452

Asia WGS AF: 0.777 AC: 2694 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 22, 2019	- -

Non-ketotic hyperglycinemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs4855873; hg19: chr3-49459114;