rs1322357168

Variant names:

• chr17-7857186-C-G
• rs1322357168
• NM_001320925.4:c.94G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16686466).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320925.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA38	NM_001320925.4	MANE Select	c.94G>C	p.Glu32Gln	missense	Exon 2 of 3	NP_001307854.1	Q9BRA0-1
	NAA38	NM_032356.6		c.238G>C	p.Glu80Gln	missense	Exon 1 of 2	NP_115732.2
	NAA38	NM_001320924.3		c.94G>C	p.Glu32Gln	missense	Exon 2 of 3	NP_001307853.1	I3L3Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA38	ENST00000575771.6	TSL:1 MANE Select	c.94G>C	p.Glu32Gln	missense	Exon 2 of 3	ENSP00000460172.2	Q9BRA0-1
	NAA38	ENST00000333775.9	TSL:1	c.238G>C	p.Glu80Gln	missense	Exon 1 of 2	ENSP00000332103.5	Q9BRA0-2
	NAA38	ENST00000575071.5	TSL:2	c.94G>C	p.Glu32Gln	missense	Exon 2 of 3	ENSP00000460841.2	I3L3Z2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460808 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726688

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.094
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.11
Sift	Benign	0.038	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.098		Loss of stability (P = 0.1743)
MVP		0.28
MPC		0.58
ClinPred		0.84	D
GERP RS		5.4
PromoterAI		-0.023	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.18
gMVP		0.31
Mutation Taster		=247/53	polymorphism

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

Other links and lift over

dbSNP: rs1322357168; hg19: chr17-7760504;