Genetic Variant NM_001320925.4:c.94G>C (chr17-7857186-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320925.4(NAA38):c.94G>C(p.Glu32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NAA38
NM_001320925.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16686466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA38	NM_001320925.4 link	c.94G>C	p.Glu32Gln	missense_variant	Exon 2 of 3	ENST00000575771.6	NP_001307854.1	Q9BRA0-1
NAA38	NM_032356.6 link	c.238G>C	p.Glu80Gln	missense_variant	Exon 1 of 2		NP_115732.2	Q9BRA0-2
NAA38	NM_001320924.3 link	c.94G>C	p.Glu32Gln	missense_variant	Exon 2 of 3		NP_001307853.1	I3L3Z2
NAA38	NM_001330111.2 link	c.16G>C	p.Glu6Gln	missense_variant	Exon 4 of 5		NP_001317040.1	I3L4V0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA38	ENST00000575771.6 link	c.94G>C	p.Glu32Gln	missense_variant	Exon 2 of 3	1	NM_001320925.4	ENSP00000460172.2		Q9BRA0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460808

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726688

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238G>C (p.E80Q) alteration is located in exon 1 (coding exon 1) of the NAA38 gene. This alteration results from a G to C substitution at nucleotide position 238, causing the glutamic acid (E) at amino acid position 80 to be replaced by a glutamine (Q). 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

Benign

0.079

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

.;.;T;T

Eigen

Benign

0.094

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

.;.;N;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.32

.;N;.;.

REVEL

Benign

0.11

Sift

Benign

0.038

.;D;.;.

Sift4G

Uncertain

0.018

D;D;D;D

Polyphen

1.0, 0.59

.;D;P;.

Vest4

0.30

MutPred

0.098

Loss of stability (P = 0.1743);.;Loss of stability (P = 0.1743);.;

MVP

0.28

MPC

0.58

ClinPred

0.84

GERP RS

5.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.18

gMVP

0.31

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

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