Variant chr3-49422364-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000481.4(AMT):c.87A>G(p.Ala29Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,610,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AMT
NM_000481.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.829

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]

AMT links:

NICN1 (HGNC:18317): (nicolin 1, tubulin polyglutamylase complex subunit) This protein encoded by this gene localizes to the nucleus and is expressed in numerous tissues including brain, testis, liver, and kidney. This refseq contains genomic sequence in its 3' UTR which is not supported by experimental evidence. Computer predictions indicate that this region of the 3' UTR contains hairpin-forming self-complementary sequence which is possibly excised after transcription. This gene has a pseudogene on chromosome X. [provided by RefSeq, Jul 2008]

NICN1 links:

ENSG00000283189 (HGNC:):

ENSG00000283189 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-49422364-T-C is Benign according to our data. Variant chr3-49422364-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2126729.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.829 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMT	NM_000481.4 linkuse as main transcript	c.87A>G	p.Ala29Ala	synonymous_variant	1/9	ENST00000273588.9	NP_000472.2	P48728-1A0A024R2U7
NICN1	NM_032316.3 linkuse as main transcript	c.*2469A>G		3_prime_UTR_variant	6/6	ENST00000273598.8	NP_115692.1	Q9BSH3-1B2R7Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMT	ENST00000273588.9 linkuse as main transcript	c.87A>G	p.Ala29Ala	synonymous_variant	1/9	1	NM_000481.4	ENSP00000273588.3	P48728-1
NICN1	ENST00000273598 linkuse as main transcript	c.*2469A>G		3_prime_UTR_variant	6/6	1	NM_032316.3	ENSP00000273598.4	Q9BSH3-1
ENSG00000283189	ENST00000636166.1 linkuse as main transcript	c.496-792A>G		intron_variant		5		ENSP00000490106.1	A0A1B0GUH1

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251148

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726278

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150734

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73644

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Glycine encephalopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 31, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.2

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over