1-109985071-A-C

Position:

• chr1-109985071-A-C

Variant summary

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

The NM_001242673.2(AHCYL1):​c.-494A>C variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHCYL1 NM_001242673.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

Genes affected

AHCYL1 (HGNC:344): (adenosylhomocysteinase like 1) The protein encoded by this gene interacts with inositol 1,4,5-trisphosphate receptor, type 1 and may be involved in the conversion of S-adenosyl-L-homocysteine to L-homocysteine and adenosine. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

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=0.18488553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCYL1	NM_006621.7	c.19A>C	p.Met7Leu	missense_variant	1/17	ENST00000369799.10	NP_006612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCYL1	ENST00000369799.10	c.19A>C	p.Met7Leu	missense_variant	1/17	1	NM_006621.7	ENSP00000358814.5
AHCYL1	ENST00000393614	c.-494A>C		5_prime_UTR_premature_start_codon_gain_variant	1/17	2		ENSP00000377238.4
AHCYL1	ENST00000393614	c.-494A>C		5_prime_UTR_variant	1/17	2		ENSP00000377238.4
AHCYL1	ENST00000475081.1	n.57A>C		non_coding_transcript_exon_variant	1/7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Sep 27, 2024

The c.19A>C (p.M7L) alteration is located in exon 1 (coding exon 1) of the AHCYL1 gene. This alteration results from a A to C substitution at nucleotide position 19, causing the methionine (M) at amino acid position 7 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	0.072
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.24	N
REVEL	Uncertain	0.37
Sift	Benign	0.43	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.46
MutPred		0.19		Gain of catalytic residue at M7 (P = 0.066);
MVP		0.82
MPC		1.1
ClinPred		0.31	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.21

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: chr1-110527693;