17-7857408-C-G

Variant names:

• chr17-7857408-C-G
• rs1246772868
• NM_001320925.4:c.56G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001320925.4(NAA38):​c.56G>C​(p.Arg19Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,447,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NAA38 NM_001320925.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA38	NM_001320925.4	c.56G>C	p.Arg19Pro	missense_variant	Exon 1 of 3	ENST00000575771.6	NP_001307854.1
NAA38	NM_032356.6	c.16G>C	p.Gly6Arg	missense_variant	Exon 1 of 2		NP_115732.2
NAA38	NM_001320924.3	c.56G>C	p.Arg19Pro	missense_variant	Exon 1 of 3		NP_001307853.1
NAA38	NM_001330111.2	c.4-210G>C		intron_variant	Intron 3 of 4		NP_001317040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA38	ENST00000575771.6	c.56G>C	p.Arg19Pro	missense_variant	Exon 1 of 3	1	NM_001320925.4	ENSP00000460172.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447778 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720280

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000395

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: 0.0000167

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16G>C (p.G6R) 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 16, causing the glycine (G) at amino acid position 6 to be replaced by an arginine (R). 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	0.087
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.50	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.33
MutPred		0.48		Gain of methylation at G6 (P = 0.0182);
MVP		0.81
MPC		1.6
ClinPred		1.0	D
GERP RS		5.5
gMVP		0.17

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

Other links and lift over

dbSNP: rs1246772868; hg19: chr17-7760726;