Variant 7-129225254-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.178C>T(p.Pro60Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000178 in 1,456,436 control chromosomes in the GnomAD database, including 2 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 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

AHCYL2
NM_015328.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

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=0.01913619).

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHCYL2	NM_015328.4 linkuse as main transcript	c.178C>T	p.Pro60Ser	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.178C>T	p.Pro60Ser	missense_variant	1/17	1	NM_015328.4		Q96HN2-1
AHCYL2	ENST00000446544.6 linkuse as main transcript	c.178C>T	p.Pro60Ser	missense_variant	1/17	1			Q96HN2-2

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00257

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000886

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000534

AC:

AN:

63696

Hom.:

AF XY:

0.000642

AC XY:

AN XY:

37396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000918

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000996

Gnomad FIN exome

AF:

0.00340

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.000556

GnomAD4 exome

AF:

0.000168

AC:

219

AN:

1304738

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

121

AN XY:

643062

show subpopulations

Gnomad4 AFR exome

AF:

0.0000389

Gnomad4 AMR exome

AF:

0.0000902

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000850

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.0000574

Gnomad4 OTH exome

AF:

0.000870

GnomAD4 genome

AF:

0.000264

AC:

AN:

151698

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00257

Gnomad4 NFE

AF:

0.0000886

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000605

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

Sep 16, 2021

The c.178C>T (p.P60S) 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 178, causing the proline (P) at amino acid position 60 to be replaced by a serine (S). 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

0.077

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.084

T;.

Eigen

Benign

-0.025

Eigen_PC

Benign

0.063

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.68

T;T

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

-0.34

N;N

MutationTaster

Benign

0.75

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.20

Sift

Benign

0.94

T;T

Sift4G

Uncertain

0.032

D;D

Polyphen

0.49

P;P

Vest4

0.28

MVP

0.18

MPC

1.6

ClinPred

0.14

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.18

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