20-20027937-T-C

Variant names:

• chr20-20027937-T-C
• rs6081840
• NM_016100.5:c.305+1018T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016100.5(NAA20):​c.305+1018T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,000 control chromosomes in the GnomAD database, including 10,324 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 0.34 (10324 hom., cov: 31)
• Consequence: NAA20 NM_016100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016100.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA20	NM_016100.5	MANE Select	c.305+1018T>C		intron	N/A	NP_057184.1
	NAA20	NM_181527.3		c.269+1018T>C		intron	N/A	NP_852668.1
	NAA20	NM_181528.3		c.305+1018T>C		intron	N/A	NP_852669.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA20	ENST00000334982.9	TSL:1 MANE Select	c.305+1018T>C		intron	N/A	ENSP00000335636.4
	NAA20	ENST00000398602.2	TSL:5	c.269+1018T>C		intron	N/A	ENSP00000381603.2
	NAA20	ENST00000310450.8	TSL:2	c.305+1018T>C		intron	N/A	ENSP00000311027.4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51129 AN: 151878 Hom.: 10324 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.336 AC: 51119 AN: 152000 Hom.: 10324 Cov.: 31 AF XY: 0.335 AC XY: 24874 AN XY: 74272

African (AFR) AF: 0.117 AC: 4842 AN: 41492

American (AMR) AF: 0.343 AC: 5232 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1442 AN: 3472

East Asian (EAS) AF: 0.116 AC: 600 AN: 5176

South Asian (SAS) AF: 0.376 AC: 1811 AN: 4818

European-Finnish (FIN) AF: 0.504 AC: 5306 AN: 10526

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30451 AN: 67946

Other (OTH) AF: 0.338 AC: 713 AN: 2108

Alfa AF: 0.400 Hom.: 9286

Bravo AF: 0.314

Asia WGS AF: 0.236 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.85
PhyloP100		-0.083
Mutation Taster		=100/0	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: rs6081840; hg19: chr20-20008581;