rs819156

Variant names:

• chr20-34293217-A-C
• rs819156
• NM_000687.4:c.296-710T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-34293217-A-C
• chr20-34293217-A-G

Variant summary

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

The NM_000687.4(AHCY):​c.296-710T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,002 control chromosomes in the GnomAD database, including 57,740 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 0.87 (57740 hom., cov: 30)
• Consequence: AHCY NM_000687.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 5 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: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHCY	NM_000687.4	c.296-710T>G		intron_variant	Intron 3 of 9	ENST00000217426.7	NP_000678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHCY	ENST00000217426.7	c.296-710T>G		intron_variant	Intron 3 of 9	1	NM_000687.4	ENSP00000217426.2

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132288 AN: 151884 Hom.: 57691 Cov.: 30

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.871 AC: 132392 AN: 152002 Hom.: 57740 Cov.: 30 AF XY: 0.869 AC XY: 64560 AN XY: 74264

African (AFR) AF: 0.851 AC: 35286 AN: 41452

American (AMR) AF: 0.911 AC: 13901 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2843 AN: 3470

East Asian (EAS) AF: 0.782 AC: 4021 AN: 5140

South Asian (SAS) AF: 0.799 AC: 3846 AN: 4812

European-Finnish (FIN) AF: 0.877 AC: 9273 AN: 10570

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60344 AN: 67982

Other (OTH) AF: 0.865 AC: 1827 AN: 2112

Alfa AF: 0.876 Hom.: 10179

Bravo AF: 0.875

Asia WGS AF: 0.809 AC: 2813 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		0.017
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs819156; hg19: chr20-32881023;