20-34301898-C-T

Variant names:

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

Variant summary

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

The NM_000687.4(AHCY):​c.28+1345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 985,260 control chromosomes in the GnomAD database, including 370,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (44138 hom., cov: 33)
  • Exomes 𝑓: 0.88 (326566 hom.)
• Consequence: AHCY NM_000687.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-34301898-C-T is Benign according to our data. Variant chr20-34301898-C-T is described in ClinVar as Benign. ClinVar VariationId is 1188863.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_000687.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCY	NM_000687.4	MANE Select	c.28+1345G>A		intron	N/A	NP_000678.1
	AHCY	NM_001322086.2		c.-118G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001309015.1
	AHCY	NM_001322084.2		c.-197G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001309013.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCY	ENST00000217426.7	TSL:1 MANE Select	c.28+1345G>A		intron	N/A	ENSP00000217426.2
	AHCY	ENST00000468908.1	TSL:5	n.51G>A		non_coding_transcript_exon	Exon 1 of 5
	AHCY	ENST00000538132.1	TSL:2	c.-56-6313G>A		intron	N/A	ENSP00000442820.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109841 AN: 152070 Hom.: 44109 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.764

GnomAD4 exome AF: 0.881 AC: 734198 AN: 833072 Hom.: 326566 Cov.: 33 AF XY: 0.882 AC XY: 339312 AN XY: 384690

African (AFR) AF: 0.285 AC: 4502 AN: 15784

American (AMR) AF: 0.905 AC: 891 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 4319 AN: 5150

East Asian (EAS) AF: 0.776 AC: 2817 AN: 3630

South Asian (SAS) AF: 0.798 AC: 13135 AN: 16458

European-Finnish (FIN) AF: 0.881 AC: 252 AN: 286

Middle Eastern (MID) AF: 0.776 AC: 1257 AN: 1620

European-Non Finnish (NFE) AF: 0.898 AC: 684078 AN: 761858

Other (OTH) AF: 0.840 AC: 22947 AN: 27302

GnomAD4 genome AF: 0.722 AC: 109910 AN: 152188 Hom.: 44138 Cov.: 33 AF XY: 0.725 AC XY: 53965 AN XY: 74428

African (AFR) AF: 0.337 AC: 13987 AN: 41472

American (AMR) AF: 0.849 AC: 12998 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2832 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4061 AN: 5180

South Asian (SAS) AF: 0.796 AC: 3841 AN: 4824

European-Finnish (FIN) AF: 0.877 AC: 9304 AN: 10612

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

European-Non Finnish (NFE) AF: 0.886 AC: 60231 AN: 68010

Other (OTH) AF: 0.765 AC: 1615 AN: 2112

Alfa AF: 0.696 Hom.: 11740

Bravo AF: 0.705

Asia WGS AF: 0.779 AC: 2707 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		-0.35
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: rs819147; hg19: chr20-32889704;