chr20-20026871-T-C

Position:

• chr20-20026871-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_016100.5(NAA20):​c.257T>C​(p.Leu86Pro) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAA20 NM_016100.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

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 6 ACMG points.

• 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, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA20	NM_016100.5	c.257T>C	p.Leu86Pro	missense_variant	4/6	ENST00000334982.9
NAA20	NM_181527.3	c.221T>C	p.Leu74Pro	missense_variant	4/6
NAA20	NM_181528.3	c.257T>C	p.Leu86Pro	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA20	ENST00000334982.9	c.257T>C	p.Leu86Pro	missense_variant	4/6	1	NM_016100.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

The c.257T>C (p.L86P) alteration is located in exon 4 (coding exon 4) of the NAA20 gene. This alteration results from a T to C substitution at nucleotide position 257, causing the leucine (L) at amino acid position 86 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T;.;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.6	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.3	D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.96	P;.;D
Vest4		0.92
MutPred		0.55		Loss of stability (P = 0.0397);Loss of stability (P = 0.0397);.;
MVP		0.69
MPC		1.8
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.94
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-20007515;