Variant chr2-73641545-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003960.4(NAT8):c.84T>A(p.His28Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,610,478 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 109 hom. )

Consequence

NAT8
NM_003960.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.217

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:29586): (ALMS1 pseudogene 1)

ALMS1P1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020417273).

BP6

Variant 2-73641545-A-T is Benign according to our data. Variant chr2-73641545-A-T is described in ClinVar as [Benign]. Clinvar id is 790819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT8	NM_003960.4 linkuse as main transcript	c.84T>A	p.His28Gln	missense_variant	2/2	ENST00000272425.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT8	ENST00000272425.4 linkuse as main transcript	c.84T>A	p.His28Gln	missense_variant	2/2	1	NM_003960.4	P1
ALMS1P1	ENST00000652439.1 linkuse as main transcript	n.243+220A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

406

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0726

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00633

AC:

1565

AN:

247094

Hom.:

AF XY:

0.00584

AC XY:

779

AN XY:

133478

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0811

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000423

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00417

GnomAD4 exome

AF:

0.00207

AC:

3020

AN:

1458244

Hom.:

109

Cov.:

AF XY:

0.00202

AC XY:

1464

AN XY:

725202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.0648

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.000714

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00433

GnomAD4 genome

AF:

0.00268

AC:

408

AN:

152234

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0729

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000293

Hom.:

Bravo

AF:

0.00326

ExAC

AF:

0.00600

AC:

729

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.5

DANN

Benign

0.78

DEOGEN2

Benign

0.30

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-5.6

REVEL

Benign

0.12

Sift

Benign

0.083

Sift4G

Benign

0.18

Polyphen

0.43

Vest4

0.24

MutPred

0.51

Loss of methylation at R23 (P = 0.1122);

MVP

0.44

MPC

0.0076

ClinPred

0.055

GERP RS

-0.82

Varity_R

0.13

gMVP

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over