20-34278756-C-T

Variant names:

• chr20-34278756-C-T
• rs819173
• XM_017027709.3:c.*8-587G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000512005.1(ENSG00000250917):​n.147+2271G>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: ENSG00000250917 ENST00000512005.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000250917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512005.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250917	ENST00000512005.1	TSL:3	n.147+2271G>A		intron	N/A

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

African (AFR) AF: 0.446 AC: 18447 AN: 41350

American (AMR) AF: 0.861 AC: 13142 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2830 AN: 3466

East Asian (EAS) AF: 0.783 AC: 4048 AN: 5170

South Asian (SAS) AF: 0.798 AC: 3833 AN: 4804

European-Finnish (FIN) AF: 0.877 AC: 9274 AN: 10574

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60290 AN: 68002

Other (OTH) AF: 0.787 AC: 1662 AN: 2112

Alfa AF: 0.848 Hom.: 88833

Bravo AF: 0.741

Asia WGS AF: 0.790 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.9
DANN	Benign	0.83
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs819173; hg19: chr20-32866562;