2-73641132-C-G

Variant summary

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

The NM_003960.4(NAT8):ā€‹c.497G>Cā€‹(p.Arg166Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R166W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NAT8
NM_003960.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25
Variant links:
Genes affected
NAT8 (HGNC:18069): (N-acetyltransferase 8 (putative)) This gene, isolated using the differential display method to detect tissue-specific genes, is specifically expressed in kidney and liver. The encoded protein shows amino acid sequence similarity to N-acetyltransferases. A similar protein in Xenopus affects cell adhesion and gastrulation movements, and may be localized in the secretory pathway. A highly similar paralog is found in a cluster with this gene. [provided by RefSeq, Sep 2008]
ALMS1P1 (HGNC:29586): (ALMS1 pseudogene 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
NAT8NM_003960.4 linkuse as main transcriptc.497G>C p.Arg166Pro missense_variant 2/2 ENST00000272425.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAT8ENST00000272425.4 linkuse as main transcriptc.497G>C p.Arg166Pro missense_variant 2/21 NM_003960.4 P1
ALMS1P1ENST00000652439.1 linkuse as main transcriptn.50C>G non_coding_transcript_exon_variant 1/7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461862
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 23, 2024The c.497G>C (p.R166P) alteration is located in exon 2 (coding exon 1) of the NAT8 gene. This alteration results from a G to C substitution at nucleotide position 497, causing the arginine (R) at amino acid position 166 to be replaced by a proline (P). 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
Pathogenic
0.68
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.063
N
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.0050
T
MetaRNN
Uncertain
0.58
D
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Pathogenic
-5.4
D
REVEL
Benign
0.18
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.37
MutPred
0.71
Loss of MoRF binding (P = 0.0166);
MVP
0.36
MPC
0.019
ClinPred
0.99
D
GERP RS
1.0
Varity_R
0.86
gMVP
0.80

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: chr2-73868259; API