3-49421819-C-G

Position:

• chr3-49421819-C-G

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.259-247G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 671,500 control chromosomes in the GnomAD database, including 81,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (13927 hom., cov: 31)
  • Exomes 𝑓: 0.48 (67127 hom.)
• Consequence: AMT NM_000481.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.352

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=-0.53).
• BP6: Variant 3-49421819-C-G is Benign according to our data. Variant chr3-49421819-C-G is described in ClinVar as [Benign]. Clinvar id is 1294488.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.259-247G>C		intron_variant		ENST00000273588.9	NP_000472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMT	ENST00000273588.9	c.259-247G>C		intron_variant		1	NM_000481.4	ENSP00000273588.3
ENSG00000283189	ENST00000636166.1	c.496-247G>C		intron_variant		5		ENSP00000490106.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59417 AN: 151894 Hom.: 13913 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.480 AC: 249180 AN: 519488 Hom.: 67127 Cov.: 5 AF XY: 0.490 AC XY: 135645 AN XY: 277036

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.672

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.933

Gnomad4 SAS exome AF: 0.660

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.391 AC: 59445 AN: 152012 Hom.: 13927 Cov.: 31 AF XY: 0.399 AC XY: 29687 AN XY: 74312

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.403

Alfa AF: 0.398 Hom.: 1583

Bravo AF: 0.398

Asia WGS AF: 0.759 AC: 2633 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	-0.53
CADD	Benign	8.1
DANN	Benign	0.70

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: rs1464567; hg19: chr3-49459252;