chr3-49417124-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000481.4(AMT):​c.*416C>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 0.000517 in 797,190 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00060 ( 3 hom. )

Consequence

AMT
NM_000481.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0100
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 3-49417124-G-A is Benign according to our data. Variant chr3-49417124-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 900802.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000603 (389/644868) while in subpopulation SAS AF= 0.00561 (359/63988). AF 95% confidence interval is 0.00513. There are 3 homozygotes in gnomad4_exome. There are 296 alleles in male gnomad4_exome subpopulation. Median coverage is 8. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AMTNM_000481.4 linkuse as main transcriptc.*416C>T 3_prime_UTR_variant 9/9 ENST00000273588.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AMTENST00000273588.9 linkuse as main transcriptc.*416C>T 3_prime_UTR_variant 9/91 NM_000481.4 P1P48728-1

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00476
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00114
AC:
152
AN:
133742
Hom.:
1
AF XY:
0.00149
AC XY:
108
AN XY:
72512
show subpopulations
Gnomad AFR exome
AF:
0.000155
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000948
Gnomad SAS exome
AF:
0.00639
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000386
Gnomad OTH exome
AF:
0.000734
GnomAD4 exome
AF:
0.000603
AC:
389
AN:
644868
Hom.:
3
Cov.:
8
AF XY:
0.000863
AC XY:
296
AN XY:
343008
show subpopulations
Gnomad4 AFR exome
AF:
0.000115
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000625
Gnomad4 SAS exome
AF:
0.00561
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000319
Gnomad4 OTH exome
AF:
0.000388
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152322
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00435
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000854
Hom.:
0
Bravo
AF:
0.0000718
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Non-ketotic hyperglycinemia Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
4.5
DANN
Benign
0.58
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs571207015; hg19: chr3-49454557; API