20-34301898-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.351

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
AHCY	NM_000687.4	c.28+1345G>A		intron_variant		ENST00000217426.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHCY	ENST00000217426.7	c.28+1345G>A		intron_variant		1	NM_000687.4	P1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109841 AN: 152070 Hom.: 44109 Cov.: 33

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.: 33 AF XY: 0.882 AC XY: 339312 AN XY: 384690

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.: 33 AF XY: 0.725 AC XY: 53965 AN XY: 74428

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Other links and lift over

dbSNP: rs819147; hg19: chr20-32889704;