3-49421943-T-C

Position:

• chr3-49421943-T-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.258+161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 980,648 control chromosomes in the GnomAD database, including 117,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15844 hom., cov: 32)
  • Exomes 𝑓: 0.47 (101575 hom.)
• Consequence: AMT NM_000481.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0830

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]

ENSG00000283189 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-49421943-T-C is Benign according to our data. Variant chr3-49421943-T-C is described in ClinVar as [Benign]. Clinvar id is 1271985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.258+161A>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.258+161A>G		intron_variant		1	NM_000481.4	ENSP00000273588.3
ENSG00000283189	ENST00000636166.1	c.496-371A>G		intron_variant		5		ENSP00000490106.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66431 AN: 151912 Hom.: 15834 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.474 AC: 392554 AN: 828618 Hom.: 101575 Cov.: 11 AF XY: 0.482 AC XY: 208941 AN XY: 433324

Gnomad4 AFR exome AF: 0.335

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.437 AC: 66473 AN: 152030 Hom.: 15844 Cov.: 32 AF XY: 0.443 AC XY: 32926 AN XY: 74308

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.440

Alfa AF: 0.438 Hom.: 24916

Bravo AF: 0.452

Asia WGS AF: 0.777 AC: 2694 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1464566; hg19: chr3-49459376;