20-34280853-G-C

Variant names:

• chr20-34280853-G-C
• rs759056638
• NM_000687.4:c.*181C>G

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.*181C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 754,838 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: AHCY NM_000687.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250917 (HGNC:):

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=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000687.4. 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
	AHCY	NM_000687.4	MANE Select	c.*181C>G		3_prime_UTR	Exon 10 of 10	NP_000678.1	A0A384MTQ3
	AHCY	NM_001322086.2		c.*181C>G		3_prime_UTR	Exon 10 of 10	NP_001309015.1
	AHCY	NM_001161766.2		c.*181C>G		3_prime_UTR	Exon 10 of 10	NP_001155238.1	P23526-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCY	ENST00000217426.7	TSL:1 MANE Select	c.*181C>G		3_prime_UTR	Exon 10 of 10	ENSP00000217426.2	P23526-1
	AHCY	ENST00000538132.1	TSL:2	c.*181C>G		3_prime_UTR	Exon 10 of 10	ENSP00000442820.1	P23526-2
	AHCY	ENST00000480653.5	TSL:2	n.1628C>G		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000132 AC: 1 AN: 754838 Hom.: 0 Cov.: 10 AF XY: 0.00000259 AC XY: 1 AN XY: 385816

African (AFR) AF: 0.0000525 AC: 1 AN: 19064

American (AMR) AF: 0.00 AC: 0 AN: 29208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17510

East Asian (EAS) AF: 0.00 AC: 0 AN: 31932

South Asian (SAS) AF: 0.00 AC: 0 AN: 57734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3010

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 529130

Other (OTH) AF: 0.00 AC: 0 AN: 36396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.79
DANN	Benign	0.57
PhyloP100		-0.83

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: rs759056638; hg19: chr20-32868659;