20-34278756-C-T

Position:

• chr20-34278756-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017027709.3(AHCY):​c.*8-587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,952 control chromosomes in the GnomAD database, including 46,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (46108 hom., cov: 30)
• Consequence: AHCY XM_017027709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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]

ENSG00000250917 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCY	XM_017027709.3	c.*8-587G>A		intron_variant			XP_016883198.1
AHCY	XM_047439962.1	c.*7+2271G>A		intron_variant			XP_047295918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000250917	ENST00000512005.1	n.147+2271G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114482 AN: 151834 Hom.: 46070 Cov.: 30

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.786

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.754 AC: 114570 AN: 151952 Hom.: 46108 Cov.: 30 AF XY: 0.756 AC XY: 56176 AN XY: 74272

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.787

Alfa AF: 0.862 Hom.: 71124

Bravo AF: 0.741

Asia WGS AF: 0.790 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.9
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs819173; hg19: chr20-32866562;