rs4239

Variant names:

• chr20-34280355-T-A
• rs4239
• NM_000687.4:c.*679A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000687.4(AHCY):​c.*679A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,146 control chromosomes in the GnomAD database, including 2,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2854 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AHCY NM_000687.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.90
• 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 20-34280355-T-A is Benign according to our data. Variant chr20-34280355-T-A is described in ClinVar as Benign. ClinVar VariationId is 338264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 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.*679A>T		3_prime_UTR	Exon 10 of 10	NP_000678.1	A0A384MTQ3
	AHCY	NM_001322086.2		c.*679A>T		3_prime_UTR	Exon 10 of 10	NP_001309015.1
	AHCY	NM_001362750.2		c.*303A>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.*679A>T		3_prime_UTR	Exon 10 of 10	ENSP00000217426.2	P23526-1
	AHCY	ENST00000538132.1	TSL:2	c.*679A>T		3_prime_UTR	Exon 10 of 10	ENSP00000442820.1	P23526-2
	AHCY	ENST00000480653.5	TSL:2	n.2126A>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16046 AN: 152028 Hom.: 2853 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0718

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 420 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 192

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 46

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 350

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.106 AC: 16060 AN: 152146 Hom.: 2854 Cov.: 32 AF XY: 0.102 AC XY: 7578 AN XY: 74398

African (AFR) AF: 0.365 AC: 15101 AN: 41408

American (AMR) AF: 0.0472 AC: 722 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68026

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0805 Hom.: 205

Bravo AF: 0.121

Asia WGS AF: 0.0160 AC: 58 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

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	-0.49
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4239; hg19: chr20-32868161;