17-7857066-G-A

Variant names:

• chr17-7857066-G-A
• NM_001320925.4:c.214C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001320925.4(NAA38):​c.214C>T​(p.Arg72Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAA38 NM_001320925.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA38	NM_001320925.4	c.214C>T	p.Arg72Cys	missense_variant	Exon 2 of 3	ENST00000575771.6	NP_001307854.1
NAA38	NM_032356.6	c.358C>T	p.Arg120Cys	missense_variant	Exon 1 of 2		NP_115732.2
NAA38	NM_001320924.3	c.214C>T	p.Arg72Cys	missense_variant	Exon 2 of 3		NP_001307853.1
NAA38	NM_001330111.2	c.136C>T	p.Arg46Cys	missense_variant	Exon 4 of 5		NP_001317040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA38	ENST00000575771.6	c.214C>T	p.Arg72Cys	missense_variant	Exon 2 of 3	1	NM_001320925.4	ENSP00000460172.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.358C>T (p.R120C) alteration is located in exon 1 (coding exon 1) of the NAA38 gene. This alteration results from a C to T substitution at nucleotide position 358, causing the arginine (R) at amino acid position 120 to be replaced by a cysteine (C). 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	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.73	.;.;D;.;D;D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.6	.;.;M;.;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-6.0	.;D;.;.;.;.
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	.;D;.;.;.;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		1.0	.;D;D;.;.;.
Vest4		0.61
MutPred		0.57		Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);.;.;.;
MVP		0.74
MPC		1.2
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.63
gMVP		0.58

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: chr17-7760384;