rs1855435303

Variant names:

• chr11-67642867-C-T
• rs1855435303
• NM_080658.2:c.817G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080658.2(ACY3):​c.817G>A​(p.Glu273Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACY3 NM_080658.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.400
• Publications: 0 publications found

Genes affected

ACY3 (HGNC:24104): (aminoacylase 3) Predicted to enable aminoacylase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30339622).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080658.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACY3	NM_080658.2	MANE Select	c.817G>A	p.Glu273Lys	missense	Exon 8 of 8	NP_542389.1	Q96HD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACY3	ENST00000255082.8	TSL:1 MANE Select	c.817G>A	p.Glu273Lys	missense	Exon 8 of 8	ENSP00000255082.3	Q96HD9
	ACY3	ENST00000897124.1		c.817G>A	p.Glu273Lys	missense	Exon 8 of 8	ENSP00000567183.1
	ACY3	ENST00000897125.1		c.817G>A	p.Glu273Lys	missense	Exon 8 of 8	ENSP00000567184.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461764 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	7.8
DANN	Benign	0.91
DEOGEN2	Uncertain	0.70	D
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.5	L
PhyloP100		-0.40
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.25
Sift	Benign	0.24	T
Sift4G	Benign	0.24	T
Polyphen		0.079	B
Vest4		0.14
MutPred		0.60		Gain of methylation at E273 (P = 0.0114)
MVP		0.76
MPC		0.15
ClinPred		0.069	T
GERP RS		1.1
Varity_R		0.097
gMVP		0.68
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1855435303; hg19: chr11-67410338;