11-34133094-C-T

Variant names:

• chr11-34133094-C-T
• rs2957518
• NM_024662.3:c.1686C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024662.3(NAT10):​c.1686C>T​(p.Pro562Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,614,020 control chromosomes in the GnomAD database, including 726,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (59009 hom., cov: 32)
  • Exomes 𝑓: 0.95 (667806 hom.)
• Consequence: NAT10 NM_024662.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.24
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-34133094-C-T is Benign according to our data. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-34133094-C-T is described in CliVar as Benign. Clinvar id is 403219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT10	NM_024662.3	c.1686C>T	p.Pro562Pro	synonymous_variant	Exon 16 of 29	ENST00000257829.8	NP_078938.3
NAT10	NM_001144030.2	c.1470C>T	p.Pro490Pro	synonymous_variant	Exon 14 of 27		NP_001137502.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT10	ENST00000257829.8	c.1686C>T	p.Pro562Pro	synonymous_variant	Exon 16 of 29	1	NM_024662.3	ENSP00000257829.3
NAT10	ENST00000531159.6	c.1470C>T	p.Pro490Pro	synonymous_variant	Exon 14 of 27	2		ENSP00000433011.2
NAT10	ENST00000527971.5	c.781-13012C>T		intron_variant	Intron 7 of 7	2		ENSP00000437324.1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132186 AN: 152104 Hom.: 58987 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.898

GnomAD2 exomes AF: 0.940 AC: 236302 AN: 251460 AF XY: 0.945

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.964

Gnomad ASJ exome AF: 0.964

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.958

Gnomad NFE exome AF: 0.958

Gnomad OTH exome AF: 0.948

GnomAD4 exome AF: 0.954 AC: 1395117 AN: 1461798 Hom.: 667806 Cov.: 53 AF XY: 0.955 AC XY: 694433 AN XY: 727210

African (AFR) AF: 0.629 AC: 21061 AN: 33472

American (AMR) AF: 0.960 AC: 42946 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 25127 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39687 AN: 39698

South Asian (SAS) AF: 0.951 AC: 82054 AN: 86254

European-Finnish (FIN) AF: 0.954 AC: 50967 AN: 53408

Middle Eastern (MID) AF: 0.932 AC: 5373 AN: 5768

European-Non Finnish (NFE) AF: 0.963 AC: 1071021 AN: 1111948

Other (OTH) AF: 0.942 AC: 56881 AN: 60392

GnomAD4 genome AF: 0.869 AC: 132252 AN: 152222 Hom.: 59009 Cov.: 32 AF XY: 0.871 AC XY: 64812 AN XY: 74426

African (AFR) AF: 0.636 AC: 26399 AN: 41490

American (AMR) AF: 0.936 AC: 14330 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3347 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5183 AN: 5188

South Asian (SAS) AF: 0.947 AC: 4567 AN: 4824

European-Finnish (FIN) AF: 0.961 AC: 10191 AN: 10602

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65193 AN: 68030

Other (OTH) AF: 0.899 AC: 1897 AN: 2110

Alfa AF: 0.917 Hom.: 34244

Bravo AF: 0.859

Asia WGS AF: 0.949 AC: 3299 AN: 3478

EpiCase AF: 0.960

EpiControl AF: 0.961

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.18
DANN	Benign	0.62
PhyloP100		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2957518; hg19: chr11-34154641; COSMIC: COSV108039371;