rs819146

Variant names:

• chr20-34303394-G-A
• rs819146
• NM_001161766.2:c.-56-7809C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-34303394-G-A
• chr20-34303394-G-C
• chr20-34303394-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001161766.2(AHCY):​c.-56-7809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 36)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AHCY NM_001161766.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 18 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHCY	NM_000687.4	c.-124C>T		upstream_gene_variant		ENST00000217426.7	NP_000678.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1227964 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 613074

African (AFR) AF: 0.00 AC: 0 AN: 28072

American (AMR) AF: 0.00 AC: 0 AN: 35268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24038

East Asian (EAS) AF: 0.00 AC: 0 AN: 34838

South Asian (SAS) AF: 0.00 AC: 0 AN: 75756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 923618

Other (OTH) AF: 0.00 AC: 0 AN: 52296

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 36 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 102392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-0.43
PromoterAI		-0.058	Neutral

Splicing

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

Other links and lift over

dbSNP: rs819146; hg19: chr20-32891200;