Variant 7-129225323-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015328.4(AHCYL2):c.247G>A(p.Ala83Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000636 in 1,493,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

AHCYL2
NM_015328.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

Variant links:

Genes affected

AHCYL2 (HGNC:22204): (adenosylhomocysteinase like 2) The protein encoded by this gene acts as a homotetramer and may be involved in the conversion of S-adenosyl-L-homocysteine to L-homocysteine and adenosine. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

AHCYL2 links:

AHCYL2 (HGNC:):

AHCYL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008054882).

BS2

High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCYL2	NM_015328.4 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/17	ENST00000325006.8	NP_056143.1	Q96HN2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCYL2	ENST00000325006.8 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/17	1	NM_015328.4	ENSP00000315931.3		Q96HN2-1
AHCYL2	ENST00000446544.6 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/17	1		ENSP00000413639.2		Q96HN2-2

Frequencies

GnomAD3 genomes

AF:

0.000395

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

90330

Hom.:

AF XY:

0.0000584

AC XY:

AN XY:

51342

show subpopulations

Gnomad AFR exome

AF:

0.00164

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1341736

Hom.:

Cov.:

AF XY:

0.0000242

AC XY:

AN XY:

661756

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.000100

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.42e-7

Gnomad4 OTH exome

AF:

0.000161

GnomAD4 genome

AF:

0.000394

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.247G>A (p.A83T) alteration is located in exon 1 (coding exon 1) of the AHCYL2 gene. This alteration results from a G to A substitution at nucleotide position 247, causing the alanine (A) at amino acid position 83 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

T;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.76

T;T

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.0081

T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.53

N;N

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.49

P;P

Vest4

0.40

MVP

0.31

MPC

0.88

ClinPred

0.20

GERP RS

4.7

Varity_R

0.42

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over