7-129225197-A-T

Position:

• chr7-129225197-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015328.4(AHCYL2):​c.121A>T​(p.Met41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: AHCYL2 NM_015328.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08140859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCYL2	NM_015328.4	c.121A>T	p.Met41Leu	missense_variant	1/17	ENST00000325006.8	NP_056143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCYL2	ENST00000325006.8	c.121A>T	p.Met41Leu	missense_variant	1/17	1	NM_015328.4	ENSP00000315931.3
AHCYL2	ENST00000446544.6	c.121A>T	p.Met41Leu	missense_variant	1/17	1		ENSP00000413639.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.121A>T (p.M41L) alteration is located in exon 1 (coding exon 1) of the AHCYL2 gene. This alteration results from a A to T substitution at nucleotide position 121, causing the methionine (M) at amino acid position 41 to be replaced by a leucine (L). 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	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.61	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.11
Sift	Benign	0.41	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.22
MutPred		0.26		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.093
MPC		0.84
ClinPred		0.11	T
GERP RS		1.9
Varity_R		0.19
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128865038;