Variant 2-73641267-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003960.4(NAT8):c.362T>C(p.Met121Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00735 in 1,614,100 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 69 hom. )

Consequence

NAT8
NM_003960.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0690

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0083195865).

BP6

Variant 2-73641267-A-G is Benign according to our data. Variant chr2-73641267-A-G is described in ClinVar as [Benign]. Clinvar id is 720099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT8	NM_003960.4 link	c.362T>C	p.Met121Thr	missense_variant	Exon 2 of 2	ENST00000272425.4	NP_003951.3	Q9UHE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT8	ENST00000272425.4 link	c.362T>C	p.Met121Thr	missense_variant	Exon 2 of 2	1	NM_003960.4	ENSP00000272425.3		Q9UHE5
ALMS1P1	ENST00000652439.1 link	n.185A>G		non_coding_transcript_exon_variant	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.00563

AC:

856

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00492

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00911

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00875

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00716

AC:

1801

AN:

251422

Hom.:

AF XY:

0.00723

AC XY:

982

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00753

AC:

11007

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00762

AC XY:

5539

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00543

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.00487

Gnomad4 NFE exome

AF:

0.00826

Gnomad4 OTH exome

AF:

0.00556

GnomAD4 genome

AF:

0.00562

AC:

856

AN:

152230

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

393

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00912

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.00875

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00774

Hom.:

Bravo

AF:

0.00519

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00774

AC:

940

Asia WGS

AF:

0.00289

AC:

AN:

3476

EpiCase

AF:

0.00796

EpiControl

AF:

0.00771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.49

DANN

Benign

0.30

DEOGEN2

Benign

0.13

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

REVEL

Benign

0.039

Sift

Benign

0.57

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.15

MVP

0.14

MPC

0.0048

ClinPred

0.0033

GERP RS

-1.9

Varity_R

0.059

gMVP

0.56

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