NM_000481.4:c.*130G>T

Variant names:

• chr3-49417410-C-A
• rs143731179
• NM_000481.4:c.*130G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000481.4(AMT):​c.*130G>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 0.00218 in 1,609,924 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (6 hom.)
• Consequence: AMT NM_000481.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0880
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-49417410-C-A is Benign according to our data. Variant chr3-49417410-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 346027.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR,Unknown gene

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.*130G>T		3_prime_UTR	Exon 9 of 9	NP_000472.2
	AMT	NM_001164710.2		c.*130G>T		3_prime_UTR	Exon 8 of 8	NP_001158182.1	P48728-3
	AMT	NM_001164711.2		c.*130G>T		3_prime_UTR	Exon 8 of 8	NP_001158183.1	P48728-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMT	ENST00000273588.9	TSL:1 MANE Select	c.*130G>T		3_prime_UTR	Exon 9 of 9	ENSP00000273588.3	P48728-1
	ENSG00000283189	ENST00000636166.1	TSL:5	c.*130G>T		3_prime_UTR	Exon 11 of 11	ENSP00000490106.1	A0A1B0GUH1
	AMT	ENST00000395338.7	TSL:1	c.1138-43G>T		intron	N/A	ENSP00000378747.2	P48728-4

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 219 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00180 AC: 444 AN: 246240 AF XY: 0.00185

Gnomad AFR exome AF: 0.000840

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00170

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00169

Gnomad NFE exome AF: 0.00294

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00225 AC: 3283 AN: 1457734 Hom.: 6 Cov.: 31 AF XY: 0.00222 AC XY: 1613 AN XY: 725128

African (AFR) AF: 0.000508 AC: 17 AN: 33478

American (AMR) AF: 0.000827 AC: 37 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000788 AC: 68 AN: 86258

European-Finnish (FIN) AF: 0.00173 AC: 86 AN: 49718

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5762

European-Non Finnish (NFE) AF: 0.00261 AC: 2905 AN: 1111646

Other (OTH) AF: 0.00212 AC: 128 AN: 60344

GnomAD4 genome AF: 0.00145 AC: 220 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00134 AC XY: 100 AN XY: 74406

African (AFR) AF: 0.000385 AC: 16 AN: 41536

American (AMR) AF: 0.000524 AC: 8 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00251 AC: 171 AN: 67994

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00172 Hom.: 0

Bravo AF: 0.00140

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Glycine encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		-0.088
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143731179; hg19: chr3-49454843;