chr20-20026853-C-T

Position:

• chr20-20026853-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1_Moderate PM1 PM2 PP3_Moderate PP5

The NM_016100.5(NAA20):​c.239C>T​(p.Ala80Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAA20 NM_016100.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.89

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PS1: Transcript NM_016100.5 (NAA20) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• PM1: In a domain N-acetyltransferase (size 155) in uniprot entity NAA20_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_016100.5
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849
• PP5: Variant 20-20026853-C-T is Pathogenic according to our data. Variant chr20-20026853-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1338748.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA20	NM_016100.5	c.239C>T	p.Ala80Val	missense_variant	4/6	ENST00000334982.9
NAA20	NM_181527.3	c.203C>T	p.Ala68Val	missense_variant	4/6
NAA20	NM_181528.3	c.239C>T	p.Ala80Val	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA20	ENST00000334982.9	c.239C>T	p.Ala80Val	missense_variant	4/6	1	NM_016100.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual developmental disorder, autosomal recessive 73 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 27, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T;.;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0010	D;T;T
Polyphen		0.85	P;.;P
Vest4		0.90
MutPred		0.54		Gain of MoRF binding (P = 0.2036);Gain of MoRF binding (P = 0.2036);.;
MVP		0.76
MPC		1.3
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-20007497;