rs948445

Variant names:

• chr11-67647021-C-A
• rs948445
• NM_080658.2:c.23G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-67647021-C-A
• chr11-67647021-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080658.2(ACY3):​c.23G>T​(p.Arg8Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACY3 NM_080658.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 35 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14316174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACY3	NM_080658.2	c.23G>T	p.Arg8Leu	missense_variant	Exon 3 of 8	ENST00000255082.8	NP_542389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACY3	ENST00000255082.8	c.23G>T	p.Arg8Leu	missense_variant	Exon 3 of 8	1	NM_080658.2	ENSP00000255082.3
ACY3	ENST00000529256.1	c.-245-96G>T		intron_variant	Intron 1 of 6	3		ENSP00000434270.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1389766 Hom.: 0 Cov.: 62 AF XY: 0.00 AC XY: 0 AN XY: 683898

African (AFR) AF: 0.00 AC: 0 AN: 31648

American (AMR) AF: 0.00 AC: 0 AN: 35166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24718

East Asian (EAS) AF: 0.00 AC: 0 AN: 35864

South Asian (SAS) AF: 0.00 AC: 0 AN: 79108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073172

Other (OTH) AF: 0.00 AC: 0 AN: 57476

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	0.022	D
MutationAssessor	Benign	1.2	L
PhyloP100		-0.066
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.24
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.65	P
Vest4		0.14
MutPred		0.32		Loss of disorder (P = 0.0303);
MVP		0.79
MPC		0.16
ClinPred		0.25	T
GERP RS		1.0
Varity_R		0.13
gMVP		0.28
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs948445; hg19: chr11-67414492;