Genetic Variant NAT10:c.373-7C>T (chr11-34113709-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_024662.3(NAT10):c.373-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,601,780 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 48 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 46 hom. )

Consequence

NAT10
NM_024662.3 splice_region, intron

Scores

Splicing: ADA: 0.0001091

Clinical Significance

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

Conservation

PhyloP100: 0.0370

Variant links:

Genes affected

NAT10 (HGNC:29830): (N-acetyltransferase 10) The protein encoded by this gene is an RNA cytidine acetyltransferase involved in histone acetylation, tRNA acetylation, the biosynthesis of 18S rRNA, and the enhancement of nuclear architecture and chromatin organization. [provided by RefSeq, Oct 2016]

NAT10 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 (BayesDel_noAF=-0.7).

BP6

Variant 11-34113709-C-T is Benign according to our data. Variant chr11-34113709-C-T is described in ClinVar as [Benign]. Clinvar id is 791313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT10	NM_024662.3 link	c.373-7C>T		splice_region_variant, intron_variant	Intron 4 of 28	ENST00000257829.8	NP_078938.3	Q9H0A0-1
NAT10	NM_001144030.2 link	c.157-7C>T		splice_region_variant, intron_variant	Intron 2 of 26		NP_001137502.2	Q9H0A0-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NAT10	ENST00000257829.8 link	c.373-7C>T	splice_region_variant, intron_variant	Intron 4 of 28	1	NM_024662.3	ENSP00000257829.3	Q9H0A0-1
NAT10	ENST00000531159.6 link	c.157-7C>T	splice_region_variant, intron_variant	Intron 2 of 26	2		ENSP00000433011.2	Q9H0A0-2
NAT10	ENST00000527971.5 link	c.373-7C>T	splice_region_variant, intron_variant	Intron 3 of 7	2		ENSP00000437324.1	E9PMU0
NAT10	ENST00000529523.5 link	c.373-7C>T	splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000435569.1	E9PJN6

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2281

AN:

150602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0529

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000885

Gnomad OTH

AF:

0.0126

GnomAD3 exomes

AF:

0.00399

AC:

996

AN:

249448

Hom.:

AF XY:

0.00298

AC XY:

402

AN XY:

134852

show subpopulations

Gnomad AFR exome

AF:

0.0546

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00155

AC:

2246

AN:

1451096

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

976

AN XY:

721852

show subpopulations

Gnomad4 AFR exome

AF:

0.0546

Gnomad4 AMR exome

AF:

0.00303

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000769

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.0153

AC:

2298

AN:

150684

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1093

AN XY:

73496

show subpopulations

Gnomad4 AFR

AF:

0.0532

Gnomad4 AMR

AF:

0.00581

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000885

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.00758

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

- -

Dec 31, 2019

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.5

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.018

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