20-34300071-C-G

Variant names:

• chr20-34300071-C-G
• rs819149
• NM_000687.4:c.28+3172G>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.28+3172G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 152,300 control chromosomes in the GnomAD database, including 76,149 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 1.0 (76149 hom., cov: 31)
• Consequence: AHCY NM_000687.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.28+3172G>C		intron	N/A	NP_000678.1	A0A384MTQ3
	AHCY	NM_001322086.2		c.34+1676G>C		intron	N/A	NP_001309015.1
	AHCY	NM_001362750.2		c.28+3172G>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.28+3172G>C		intron	N/A	ENSP00000217426.2	P23526-1
	AHCY	ENST00000538132.1	TSL:2	c.-56-4486G>C		intron	N/A	ENSP00000442820.1	P23526-2
	AHCY	ENST00000468908.1	TSL:5	n.191+1687G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152181 AN: 152182 Hom.: 76090 Cov.: 31

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

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

GnomAD4 genome AF: 1.00 AC: 152299 AN: 152300 Hom.: 76149 Cov.: 31 AF XY: 1.00 AC XY: 74463 AN XY: 74464

African (AFR) AF: 1.00 AC: 41548 AN: 41548

American (AMR) AF: 1.00 AC: 15306 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5169 AN: 5170

South Asian (SAS) AF: 1.00 AC: 4822 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68042 AN: 68042

Other (OTH) AF: 1.00 AC: 2116 AN: 2116

Alfa AF: 1.00 Hom.: 8669

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.53
PhyloP100		-1.6
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: rs819149; hg19: chr20-32887877;