1-110009101-T-C

Position:

• chr1-110009101-T-C

Variant summary

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

The NM_006621.7(AHCYL1):​c.188T>C​(p.Leu63Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHCYL1 NM_006621.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCYL1	NM_006621.7	c.188T>C	p.Leu63Ser	missense_variant	2/17	ENST00000369799.10	NP_006612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCYL1	ENST00000369799.10	c.188T>C	p.Leu63Ser	missense_variant	2/17	1	NM_006621.7	ENSP00000358814.5
AHCYL1	ENST00000359172.3	c.47T>C	p.Leu16Ser	missense_variant	2/17	1		ENSP00000352092.3
AHCYL1	ENST00000393614.8	c.47T>C	p.Leu16Ser	missense_variant	2/17	2		ENSP00000377238.4
AHCYL1	ENST00000475081.1	n.226T>C		non_coding_transcript_exon_variant	2/7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 23, 2024

The c.188T>C (p.L63S) alteration is located in exon 2 (coding exon 2) of the AHCYL1 gene. This alteration results from a T to C substitution at nucleotide position 188, causing the leucine (L) at amino acid position 63 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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;.
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	-0.0047	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.041	D;T;T
Polyphen		1.0	D;.;.
Vest4		0.58
MutPred		0.28		Gain of phosphorylation at L63 (P = 2e-04);.;.;
MVP		0.52
MPC		2.7
ClinPred		0.91	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.57

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: chr1-110551723;