3-49416844-G-A

Variant names:

• chr3-49416844-G-A
• rs10640
• NM_000481.4:c.*696C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• Publications: 33 publications found

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 Gene-Disease associations (from GenCC):

• glycine encephalopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, ClinGen
• glycine encephalopathy 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• infantile glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• neonatal glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• atypical glycine encephalopathy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000283189 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000481.4. 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
	AMT	NM_000481.4	MANE Select	c.*696C>T		3_prime_UTR	Exon 9 of 9	NP_000472.2
	AMT	NM_001164712.2		c.*500C>T		3_prime_UTR	Exon 10 of 10	NP_001158184.1	P48728-4
	AMT	NM_001164710.2		c.*696C>T		3_prime_UTR	Exon 8 of 8	NP_001158182.1	P48728-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMT	ENST00000273588.9	TSL:1 MANE Select	c.*696C>T		3_prime_UTR	Exon 9 of 9	ENSP00000273588.3	P48728-1
	ENSG00000283189	ENST00000636166.1	TSL:5	c.*696C>T		3_prime_UTR	Exon 11 of 11	ENSP00000490106.1	A0A1B0GUH1
	AMT	ENST00000395338.7	TSL:1	c.*500C>T		3_prime_UTR	Exon 10 of 10	ENSP00000378747.2	P48728-4

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43250 AN: 151730 Hom.: 6702 Cov.: 31

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

GnomAD2 exomes AF: 0.264 AC: 34458 AN: 130456 AF XY: 0.266

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 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.: 0 AF XY: 0.282 AC XY: 48638 AN XY: 172610

African (AFR) AF: 0.246 AC: 2123 AN: 8620

American (AMR) AF: 0.163 AC: 4451 AN: 27292

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 4961 AN: 10842

East Asian (EAS) AF: 0.0548 AC: 507 AN: 9258

South Asian (SAS) AF: 0.244 AC: 14531 AN: 59670

European-Finnish (FIN) AF: 0.456 AC: 5665 AN: 12426

Middle Eastern (MID) AF: 0.341 AC: 392 AN: 1150

European-Non Finnish (NFE) AF: 0.309 AC: 49302 AN: 159656

Other (OTH) AF: 0.308 AC: 4358 AN: 14140

GnomAD4 genome AF: 0.285 AC: 43272 AN: 151848 Hom.: 6707 Cov.: 31 AF XY: 0.288 AC XY: 21360 AN XY: 74246

African (AFR) AF: 0.249 AC: 10311 AN: 41390

American (AMR) AF: 0.217 AC: 3308 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3470

East Asian (EAS) AF: 0.0589 AC: 305 AN: 5182

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4822

European-Finnish (FIN) AF: 0.472 AC: 4970 AN: 10538

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20799 AN: 67886

Other (OTH) AF: 0.290 AC: 610 AN: 2106

Alfa AF: 0.300 Hom.: 9625

Bravo AF: 0.263

Asia WGS AF: 0.144 AC: 507 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Glycine encephalopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.5
DANN	Benign	0.54
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10640; hg19: chr3-49454277;