20-20025724-T-C

Variant names:

• chr20-20025724-T-C
• rs7263
• NM_016100.5:c.126T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016100.5(NAA20):​c.126T>C​(p.Tyr42Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,610,282 control chromosomes in the GnomAD database, including 4,599 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.071 (432 hom., cov: 32)
  • Exomes 𝑓: 0.071 (4167 hom.)
• Consequence: NAA20 NM_016100.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 15 publications found

Genes affected

NAA20 (HGNC:15908): (N-alpha-acetyltransferase 20, NatB catalytic subunit) NAT5 is a component of N-acetyltransferase complex B (NatB). Human NatB performs cotranslational N(alpha)-terminal acetylation of methionine residues when they are followed by asparagine (Starheim et al., 2008 [PubMed 18570629]).[supplied by OMIM, Apr 2009]

NAA20 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal recessive 73

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.064 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA20	NM_016100.5	c.126T>C	p.Tyr42Tyr	synonymous_variant	Exon 3 of 6	ENST00000334982.9	NP_057184.1
NAA20	NM_181527.3	c.90T>C	p.Tyr30Tyr	synonymous_variant	Exon 3 of 6		NP_852668.1
NAA20	NM_181528.3	c.126T>C	p.Tyr42Tyr	synonymous_variant	Exon 3 of 5		NP_852669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA20	ENST00000334982.9	c.126T>C	p.Tyr42Tyr	synonymous_variant	Exon 3 of 6	1	NM_016100.5	ENSP00000335636.4

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10754 AN: 152154 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.0780

GnomAD2 exomes AF: 0.0785 AC: 19738 AN: 251418 AF XY: 0.0768

Gnomad AFR exome AF: 0.0666

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.0832

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.0260

Gnomad NFE exome AF: 0.0711

Gnomad OTH exome AF: 0.0771

GnomAD4 exome AF: 0.0713 AC: 104022 AN: 1458010 Hom.: 4167 Cov.: 30 AF XY: 0.0713 AC XY: 51729 AN XY: 725548

African (AFR) AF: 0.0709 AC: 2367 AN: 33386

American (AMR) AF: 0.118 AC: 5289 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0800 AC: 2088 AN: 26104

East Asian (EAS) AF: 0.147 AC: 5814 AN: 39670

South Asian (SAS) AF: 0.0792 AC: 6826 AN: 86158

European-Finnish (FIN) AF: 0.0300 AC: 1603 AN: 53416

Middle Eastern (MID) AF: 0.0437 AC: 252 AN: 5762

European-Non Finnish (NFE) AF: 0.0682 AC: 75556 AN: 1108554

Other (OTH) AF: 0.0702 AC: 4227 AN: 60250

GnomAD4 genome AF: 0.0708 AC: 10779 AN: 152272 Hom.: 432 Cov.: 32 AF XY: 0.0692 AC XY: 5151 AN XY: 74470

African (AFR) AF: 0.0695 AC: 2886 AN: 41538

American (AMR) AF: 0.0989 AC: 1513 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3468

East Asian (EAS) AF: 0.112 AC: 582 AN: 5180

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4828

European-Finnish (FIN) AF: 0.0230 AC: 244 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0684 AC: 4656 AN: 68022

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0725 Hom.: 1941

Bravo AF: 0.0767

Asia WGS AF: 0.107 AC: 371 AN: 3478

EpiCase AF: 0.0707

EpiControl AF: 0.0687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.9
DANN	Benign	0.29
PhyloP100		-0.064
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs7263; hg19: chr20-20006368; COSMIC: COSV58549442; COSMIC: COSV58549442;