Genetic Variant NAA38:p.Trp56* (chr17-7857256-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_032356.6(NAA38):c.168G>A(p.Trp56*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,610,054 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 15 hom., cov: 32)

Exomes 𝑓: 0.013 ( 142 hom. )

Consequence

NAA38
NM_032356.6 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

NAA38 (HGNC:28212): (N-alpha-acetyltransferase 38, NatC auxiliary subunit) Involved in negative regulation of apoptotic process. Located in cytoplasm and nucleoplasm. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]

NAA38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 17-7857256-C-T is Benign according to our data. Variant chr17-7857256-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 808218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1366 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA38	NM_001320925.4 link	c.82-58G>A		intron_variant	Intron 1 of 2	ENST00000575771.6	NP_001307854.1	Q9BRA0-1
NAA38	NM_032356.6 link	c.168G>A	p.Trp56*	stop_gained	Exon 1 of 2		NP_115732.2	Q9BRA0-2
NAA38	NM_001320924.3 link	c.82-58G>A		intron_variant	Intron 1 of 2		NP_001307853.1	I3L3Z2
NAA38	NM_001330111.2 link	c.4-58G>A		intron_variant	Intron 3 of 4		NP_001317040.1	I3L4V0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA38	ENST00000575771.6 link	c.82-58G>A		intron_variant	Intron 1 of 2	1	NM_001320925.4	ENSP00000460172.2		Q9BRA0-1

Frequencies

GnomAD3 genomes

AF:

0.00898

AC:

1366

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00926

AC:

2227

AN:

240582

Hom.:

AF XY:

0.00967

AC XY:

1277

AN XY:

132124

show subpopulations

Gnomad AFR exome

AF:

0.00287

Gnomad AMR exome

AF:

0.00644

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00263

Gnomad FIN exome

AF:

0.00224

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0125

AC:

18268

AN:

1457804

Hom.:

142

Cov.:

AF XY:

0.0124

AC XY:

8982

AN XY:

724646

show subpopulations

Gnomad4 AFR exome

AF:

0.00248

Gnomad4 AMR exome

AF:

0.00691

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00297

Gnomad4 FIN exome

AF:

0.00299

Gnomad4 NFE exome

AF:

0.0147

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00897

AC:

1366

AN:

152250

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

618

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.00823

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.0143

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00921

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00185

AC:

ESP6500EA

AF:

0.0135

AC:

114

ExAC

AF:

0.00895

AC:

1078

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0178

EpiControl

AF:

0.0202

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.60

CADD

Benign

DANN

Uncertain

0.99

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.89

Vest4

0.12

GERP RS

5.3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over