rs819147

Variant names:

• chr20-34301898-C-A
• rs819147
• NM_000687.4:c.28+1345G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-34301898-C-A
• chr20-34301898-C-T

Variant summary

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

The NM_000687.4(AHCY):​c.28+1345G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AHCY NM_000687.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• 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: 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=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHCY	NM_000687.4	c.28+1345G>T		intron_variant	Intron 1 of 9	ENST00000217426.7	NP_000678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHCY	ENST00000217426.7	c.28+1345G>T		intron_variant	Intron 1 of 9	1	NM_000687.4	ENSP00000217426.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000240 AC: 2 AN: 833118 Hom.: 0 Cov.: 33 AF XY: 0.00000260 AC XY: 1 AN XY: 384718

African (AFR) AF: 0.00 AC: 0 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.00 AC: 0 AN: 16460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.00000263 AC: 2 AN: 761898

Other (OTH) AF: 0.00 AC: 0 AN: 27302

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 11740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs819147; hg19: chr20-32889704;