rs7271501

Positions:

• chr20-34290675-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000687.4(AHCY):​c.767-37C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,613,752 control chromosomes in the GnomAD database, including 5,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2867 hom., cov: 32)
  • Exomes 𝑓: 0.011 (2640 hom.)
• Consequence: AHCY NM_000687.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.656

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-34290675-G-C is Benign according to our data. Variant chr20-34290675-G-C is described in ClinVar as [Benign]. Clinvar id is 471683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCY	NM_000687.4	c.767-37C>G		intron_variant		ENST00000217426.7	NP_000678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCY	ENST00000217426.7	c.767-37C>G		intron_variant		1	NM_000687.4	ENSP00000217426	P1
AHCY	ENST00000538132.1	c.683-37C>G		intron_variant		2		ENSP00000442820
AHCY	ENST00000480653.5	n.814-37C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16070 AN: 151998 Hom.: 2866 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0470

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: 0.0727

GnomAD3 exomes AF: 0.0271 AC: 6806 AN: 251332 Hom.: 1142 AF XY: 0.0203 AC XY: 2758 AN XY: 135844

Gnomad AFR exome AF: 0.371

Gnomad AMR exome AF: 0.0169

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000947

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0108 AC: 15743 AN: 1461636 Hom.: 2640 Cov.: 34 AF XY: 0.00927 AC XY: 6741 AN XY: 727132

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.00210

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000362

Gnomad4 OTH exome AF: 0.0247

GnomAD4 genome AF: 0.106 AC: 16084 AN: 152116 Hom.: 2867 Cov.: 32 AF XY: 0.102 AC XY: 7578 AN XY: 74348

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0543 Hom.: 219

Bravo AF: 0.121

Asia WGS AF: 0.0160 AC: 58 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	This variant is associated with the following publications: (PMID: 19619139) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs7271501; hg19: chr20-32878481;