Genetic Variant NAT8:p.Gly178Cys (chr2-73641097-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003960.4(NAT8):c.532G>T(p.Gly178Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,868 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. 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. G178S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NAT8
NM_003960.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.176

Publications

0 publications found

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]

NAT8 links:

ALMS1P1 (HGNC:):

ALMS1P1 links:

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ACMG classification

Classification was made for transcript

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=0.20504713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003960.4. 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
	NAT8	NM_003960.4	MANE Select	c.532G>T	p.Gly178Cys	missense	Exon 2 of 2	NP_003951.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAT8	ENST00000272425.4	TSL:1 MANE Select	c.532G>T	p.Gly178Cys	missense	Exon 2 of 2	ENSP00000272425.3	Q9UHE5
NAT8	ENST00000852385.1		c.532G>T	p.Gly178Cys	missense	Exon 2 of 2	ENSP00000522444.1
NAT8	ENST00000852386.1		c.532G>T	p.Gly178Cys	missense	Exon 2 of 2	ENSP00000522445.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251416

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.28

M_CAP

Benign

0.0058

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

PhyloP100

-0.18

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.92

REVEL

Benign

0.075

Sift

Uncertain

0.010

Sift4G

Uncertain

0.029

Polyphen

0.62

Vest4

0.18

MutPred

0.55

Loss of catalytic residue at G178 (P = 0.0972)

MVP

0.31

MPC

0.015

ClinPred

0.94

GERP RS

-2.5

Varity_R

0.13

gMVP

0.45

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over