20-34280356-G-A

Variant names:

• chr20-34280356-G-A
• rs371150068
• NM_000687.4:c.*678C>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.*678C>T variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHCY NM_000687.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.916
• 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=-0.6).

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.*678C>T		3_prime_UTR	Exon 10 of 10	NP_000678.1	A0A384MTQ3
	AHCY	NM_001322086.2		c.*678C>T		3_prime_UTR	Exon 10 of 10	NP_001309015.1
	AHCY	NM_001362750.2		c.*302C>T		3_prime_UTR	Exon 11 of 11	NP_001349679.1	A0A384MTQ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCY	ENST00000217426.7	TSL:1 MANE Select	c.*678C>T		3_prime_UTR	Exon 10 of 10	ENSP00000217426.2	P23526-1
	AHCY	ENST00000538132.1	TSL:2	c.*678C>T		3_prime_UTR	Exon 10 of 10	ENSP00000442820.1	P23526-2
	AHCY	ENST00000480653.5	TSL:2	n.2125C>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		0.92

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: rs371150068; hg19: chr20-32868162;