chr20-34282508-T-G

Variant names:

• chr20-34282508-T-G
• rs819133
• NM_000687.4:c.1168-1343A>C

Variant summary

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

The NM_000687.4(AHCY):​c.1168-1343A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,114 control chromosomes in the GnomAD database, including 46,110 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 0.75 (46110 hom., cov: 33)
• Consequence: AHCY NM_000687.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000272945 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

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.1168-1343A>C		intron	N/A	NP_000678.1	A0A384MTQ3
	AHCY	NM_001322086.2		c.1174-1343A>C		intron	N/A	NP_001309015.1
	AHCY	NM_001362750.2		c.1168-1343A>C		intron	N/A	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.1168-1343A>C		intron	N/A	ENSP00000217426.2	P23526-1
	AHCY	ENST00000538132.1	TSL:2	c.1084-1343A>C		intron	N/A	ENSP00000442820.1	P23526-2
	AHCY	ENST00000480653.5	TSL:2	n.1316-1343A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114508 AN: 151996 Hom.: 46072 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.753 AC: 114595 AN: 152114 Hom.: 46110 Cov.: 33 AF XY: 0.756 AC XY: 56223 AN XY: 74380

African (AFR) AF: 0.444 AC: 18410 AN: 41428

American (AMR) AF: 0.860 AC: 13164 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2834 AN: 3470

East Asian (EAS) AF: 0.783 AC: 4059 AN: 5182

South Asian (SAS) AF: 0.797 AC: 3839 AN: 4818

European-Finnish (FIN) AF: 0.877 AC: 9293 AN: 10596

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60289 AN: 68002

Other (OTH) AF: 0.786 AC: 1661 AN: 2112

Alfa AF: 0.722 Hom.: 2693

Bravo AF: 0.740

Asia WGS AF: 0.790 AC: 2748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.68
PhyloP100		-0.83
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: rs819133; hg19: chr20-32870314;