Variant 7-129225306-C-T 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.230C>T(p.Ala77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000518 in 1,479,016 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

AHCYL2
NM_015328.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017946988).

BS2

High AC in GnomAd at 131 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHCYL2	NM_015328.4 linkuse as main transcript	c.230C>T	p.Ala77Val	missense_variant	1/17	ENST00000325006.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHCYL2	ENST00000325006.8 linkuse as main transcript	c.230C>T	p.Ala77Val	missense_variant	1/17	1	NM_015328.4		Q96HN2-1
AHCYL2	ENST00000446544.6 linkuse as main transcript	c.230C>T	p.Ala77Val	missense_variant	1/17	1			Q96HN2-2

Frequencies

GnomAD3 genomes

AF:

0.000862

AC:

131

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00623

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000795

AC:

AN:

80484

Hom.:

AF XY:

0.000670

AC XY:

AN XY:

46280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00718

Gnomad NFE exome

AF:

0.000691

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.000478

AC:

635

AN:

1327080

Hom.:

Cov.:

AF XY:

0.000529

AC XY:

346

AN XY:

654230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000373

Gnomad4 AMR exome

AF:

0.000188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00514

Gnomad4 NFE exome

AF:

0.000410

Gnomad4 OTH exome

AF:

0.000472

GnomAD4 genome

AF:

0.000862

AC:

131

AN:

151936

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00623

Gnomad4 NFE

AF:

0.000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000378

ExAC

AF:

0.000197

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

Oct 29, 2021

The c.230C>T (p.A77V) alteration is located in exon 1 (coding exon 1) of the AHCYL2 gene. This alteration results from a C to T substitution at nucleotide position 230, causing the alanine (A) at amino acid position 77 to be replaced by a valine (V). 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

0.094

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.14

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.092

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.78

T;T

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

0.60

N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.22

Sift

Benign

0.33

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.079

B;B

Vest4

0.29

MVP

0.35

MPC

1.4

ClinPred

0.14

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.31

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