rs819146

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001161766.2(AHCY):​c.-56-7809C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 1,379,294 control chromosomes in the GnomAD database, including 510,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (44081 hom., cov: 36)
  • Exomes 𝑓: 0.87 (466027 hom.)
• Consequence: AHCY NM_001161766.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-34303394-G-T is Benign according to our data. Variant chr20-34303394-G-T is described in ClinVar as Benign. ClinVar VariationId is 338286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161766.2. 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_001161766.2		c.-56-7809C>A		intron	N/A	NP_001155238.1	P23526-2
	AHCY	NM_000687.4	MANE Select	c.-124C>A		upstream_gene	N/A	NP_000678.1	A0A384MTQ3
	AHCY	NM_001362750.2		c.-124C>A		upstream_gene	N/A	NP_001349679.1	A0A384MTQ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCY	ENST00000538132.1	TSL:2	c.-56-7809C>A		intron	N/A	ENSP00000442820.1	P23526-2
	AHCY	ENST00000217426.7	TSL:1 MANE Select	c.-124C>A		upstream_gene	N/A	ENSP00000217426.2	P23526-1
	AHCY	ENST00000480653.5	TSL:2	n.-77C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109714 AN: 152172 Hom.: 44053 Cov.: 36

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.866 AC: 1063019 AN: 1227004 Hom.: 466027 Cov.: 18 AF XY: 0.865 AC XY: 529727 AN XY: 612600

African (AFR) AF: 0.310 AC: 8681 AN: 28012

American (AMR) AF: 0.904 AC: 31880 AN: 35256

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 20057 AN: 24028

East Asian (EAS) AF: 0.829 AC: 28856 AN: 34818

South Asian (SAS) AF: 0.788 AC: 59643 AN: 75694

European-Finnish (FIN) AF: 0.877 AC: 42730 AN: 48718

Middle Eastern (MID) AF: 0.761 AC: 4069 AN: 5350

European-Non Finnish (NFE) AF: 0.893 AC: 824137 AN: 922874

Other (OTH) AF: 0.822 AC: 42966 AN: 52254

GnomAD4 genome AF: 0.721 AC: 109780 AN: 152290 Hom.: 44081 Cov.: 36 AF XY: 0.724 AC XY: 53899 AN XY: 74466

African (AFR) AF: 0.333 AC: 13852 AN: 41538

American (AMR) AF: 0.849 AC: 12986 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2832 AN: 3472

East Asian (EAS) AF: 0.783 AC: 4050 AN: 5170

South Asian (SAS) AF: 0.796 AC: 3843 AN: 4826

European-Finnish (FIN) AF: 0.877 AC: 9313 AN: 10622

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60252 AN: 68038

Other (OTH) AF: 0.762 AC: 1611 AN: 2114

Alfa AF: 0.807 Hom.: 102392

Bravo AF: 0.704

Asia WGS AF: 0.776 AC: 2699 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypermethioninemia (1)
-	-	1	Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		-0.43
PromoterAI		0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV54152776; COSMIC: COSV54152776;