Variant 20-34301898-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000687.4(AHCY):c.28+1345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 985,260 control chromosomes in the GnomAD database, including 370,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 44138 hom., cov: 33)

Exomes 𝑓: 0.88 ( 326566 hom. )

Consequence

AHCY
NM_000687.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.351

Variant links:

Genes affected

AHCY (HGNC:343): (adenosylhomocysteinase) S-adenosylhomocysteine hydrolase belongs to the adenosylhomocysteinase family. It catalyzes the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to adenosine (Ado) and L-homocysteine (Hcy). Thus, it regulates the intracellular S-adenosylhomocysteine (SAH) concentration thought to be important for transmethylation reactions. Deficiency in this protein is one of the different causes of hypermethioninemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

AHCY links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 20-34301898-C-T is Benign according to our data. Variant chr20-34301898-C-T is described in ClinVar as [Benign]. Clinvar id is 1188863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCY	NM_000687.4 linkuse as main transcript	c.28+1345G>A		intron_variant		ENST00000217426.7	NP_000678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCY	ENST00000217426.7 linkuse as main transcript	c.28+1345G>A		intron_variant		1	NM_000687.4	ENSP00000217426	P1	P23526-1

Frequencies

GnomAD3 genomes

AF:

0.722

AC:

109841

AN:

152070

Hom.:

44109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.885

Gnomad AMR

AF:

0.849

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.795

Gnomad FIN

AF:

0.877

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.886

Gnomad OTH

AF:

0.764

GnomAD4 exome

AF:

0.881

AC:

734198

AN:

833072

Hom.:

326566

Cov.:

AF XY:

0.882

AC XY:

339312

AN XY:

384690

show subpopulations

Gnomad4 AFR exome

AF:

0.285

Gnomad4 AMR exome

AF:

0.905

Gnomad4 ASJ exome

AF:

0.839

Gnomad4 EAS exome

AF:

0.776

Gnomad4 SAS exome

AF:

0.798

Gnomad4 FIN exome

AF:

0.881

Gnomad4 NFE exome

AF:

0.898

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.722

AC:

109910

AN:

152188

Hom.:

44138

Cov.:

AF XY:

0.725

AC XY:

53965

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.849

Gnomad4 ASJ

AF:

0.816

Gnomad4 EAS

AF:

0.784

Gnomad4 SAS

AF:

0.796

Gnomad4 FIN

AF:

0.877

Gnomad4 NFE

AF:

0.886

Gnomad4 OTH

AF:

0.765

Alfa

AF:

0.685

Hom.:

4972

Bravo

AF:

0.705

Asia WGS

AF:

0.779

AC:

2707

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

DANN

Benign

0.67

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.

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