Genetic Variant AHCY:c.-56-7809C>A (chr20-34303394-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001161766.2(AHCY):c.-56-7809C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 1,379,294 control chromosomes in the GnomAD database, including 510,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 44081 hom., cov: 36)

Exomes 𝑓: 0.87 ( 466027 hom. )

Consequence

AHCY
NM_001161766.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.430

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=-0.8).

BP6

Variant 20-34303394-G-T is Benign according to our data. Variant chr20-34303394-G-T is described in ClinVar as [Benign]. Clinvar id is 338286.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 rank	MANE	Protein	UniProt
AHCY	NM_000687.4 link	c.-124C>A		upstream_gene_variant		ENST00000217426.7	NP_000678.1	P23526-1A0A384MTQ3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AHCY	ENST00000538132.1 link	c.-56-7809C>A	intron_variant	Intron 1 of 9	2		ENSP00000442820.1	P23526-2
AHCY	ENST00000217426.7 link	c.-124C>A	upstream_gene_variant		1	NM_000687.4	ENSP00000217426.2	P23526-1
AHCY	ENST00000480653.5 link	n.-77C>A	upstream_gene_variant		2
AHCY	ENST00000606061.1 link	n.-37C>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109714

AN:

152172

Hom.:

44053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.883

Gnomad AMR

AF:

0.848

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.784

Gnomad SAS

AF:

0.795

Gnomad FIN

AF:

0.877

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.886

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.866

AC:

1063019

AN:

1227004

Hom.:

466027

Cov.:

AF XY:

0.865

AC XY:

529727

AN XY:

612600

show subpopulations

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.904

Gnomad4 ASJ exome

AF:

0.835

Gnomad4 EAS exome

AF:

0.829

Gnomad4 SAS exome

AF:

0.788

Gnomad4 FIN exome

AF:

0.877

Gnomad4 NFE exome

AF:

0.893

Gnomad4 OTH exome

AF:

0.822

GnomAD4 genome

AF:

0.721

AC:

109780

AN:

152290

Hom.:

44081

Cov.:

AF XY:

0.724

AC XY:

53899

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.849

Gnomad4 ASJ

AF:

0.816

Gnomad4 EAS

AF:

0.783

Gnomad4 SAS

AF:

0.796

Gnomad4 FIN

AF:

0.877

Gnomad4 NFE

AF:

0.886

Gnomad4 OTH

AF:

0.762

Alfa

AF:

0.857

Hom.:

65120

Bravo

AF:

0.704

Asia WGS

AF:

0.776

AC:

2699

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypermethioninemia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

DANN

Benign

0.46

Splicing

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