chr7-129403413-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_015328.4(AHCYL2):c.953T>C(p.Ile318Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
AHCYL2
NM_015328.4 missense
NM_015328.4 missense
Scores
6
11
2
Clinical Significance
Conservation
PhyloP100: 7.97
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.777
BS2
?
High AC in GnomAdExome at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHCYL2 | NM_015328.4 | c.953T>C | p.Ile318Thr | missense_variant | 7/17 | ENST00000325006.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHCYL2 | ENST00000325006.8 | c.953T>C | p.Ile318Thr | missense_variant | 7/17 | 1 | NM_015328.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249584Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 134954
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GnomAD4 exome AF: 0.00000822 AC: 12AN: 1459184Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 4AN XY: 725904
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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 | Mar 12, 2024 | The c.953T>C (p.I318T) alteration is located in exon 7 (coding exon 7) of the AHCYL2 gene. This alteration results from a T to C substitution at nucleotide position 953, causing the isoleucine (I) at amino acid position 318 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;N;N;N
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;P;.;.
Vest4
MutPred
Loss of stability (P = 0.0212);.;.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at