17-7856824-C-A

Variant names:

• chr17-7856824-C-A
• NM_001320925.4:c.285G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320925.4(NAA38):​c.285G>T​(p.Glu95Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000021 (0 hom.)
• Consequence: NAA38 NM_001320925.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.462

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2981534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA38	NM_001320925.4	c.285G>T	p.Glu95Asp	missense_variant	Exon 3 of 3	ENST00000575771.6	NP_001307854.1
NAA38	NM_032356.6	c.429G>T	p.Glu143Asp	missense_variant	Exon 2 of 2		NP_115732.2
NAA38	NM_001320924.3	c.315G>T	p.Glu105Asp	missense_variant	Exon 3 of 3		NP_001307853.1
NAA38	NM_001330111.2	c.207G>T	p.Glu69Asp	missense_variant	Exon 5 of 5		NP_001317040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA38	ENST00000575771.6	c.285G>T	p.Glu95Asp	missense_variant	Exon 3 of 3	1	NM_001320925.4	ENSP00000460172.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461534 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727042

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.429G>T (p.E143D) alteration is located in exon 2 (coding exon 2) of the NAA38 gene. This alteration results from a G to T substitution at nucleotide position 429, causing the glutamic acid (E) at amino acid position 143 to be replaced by an aspartic acid (D). 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	Uncertain	0.45
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;.;T;.;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	.;.;L;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.1	.;N;.;.;.;.
REVEL	Benign	0.20
Sift	Benign	0.033	.;D;.;.;.;.
Sift4G	Benign	0.16	T;T;T;T;T;T
Polyphen		0.53, 0.33	.;P;B;.;.;.
Vest4		0.58
MutPred		0.53		.;.;Gain of sheet (P = 0.1451);.;.;.;
MVP		0.27
MPC		0.71
ClinPred		0.85	D
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7760142;