17-7857287-C-G

Variant names:

• chr17-7857287-C-G
• ENST00000333775.9:c.137G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032356.6(NAA38):​c.137G>C​(p.Cys46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 0.0000082 (0 hom.)
• Consequence: NAA38 NM_032356.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.544

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0800609).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA38	NM_001320925.4	c.82-89G>C		intron_variant	Intron 1 of 2	ENST00000575771.6	NP_001307854.1
NAA38	NM_032356.6	c.137G>C	p.Cys46Ser	missense_variant	Exon 1 of 2		NP_115732.2
NAA38	NM_001320924.3	c.82-89G>C		intron_variant	Intron 1 of 2		NP_001307853.1
NAA38	NM_001330111.2	c.4-89G>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.82-89G>C		intron_variant	Intron 1 of 2	1	NM_001320925.4	ENSP00000460172.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1459350 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 725728

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: 0.0000108

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

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.137G>C (p.C46S) 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 137, causing the cysteine (C) at amino acid position 46 to be replaced by a serine (S). 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
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.0
DANN	Benign	0.61
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.11
Sift	Benign	0.047	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0215);
MVP		0.28
MPC		0.62
ClinPred		0.50	D
GERP RS		3.3
gMVP		0.21

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: chr17-7760605;