chr17-7857408-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001320925.4(NAA38):​c.56G>T​(p.Arg19Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,778 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NAA38 NM_001320925.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• 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 2 ACMG points.

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

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.56G>T	p.Arg19Leu	missense	Exon 1 of 3	NP_001307854.1	Q9BRA0-1
	NAA38	NM_032356.6		c.16G>T	p.Gly6Cys	missense	Exon 1 of 2	NP_115732.2
	NAA38	NM_001320924.3		c.56G>T	p.Arg19Leu	missense	Exon 1 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.56G>T	p.Arg19Leu	missense	Exon 1 of 3	ENSP00000460172.2	Q9BRA0-1
	NAA38	ENST00000333775.9	TSL:1	c.16G>T	p.Gly6Cys	missense	Exon 1 of 2	ENSP00000332103.5	Q9BRA0-2
	NAA38	ENST00000575071.5	TSL:2	c.56G>T	p.Arg19Leu	missense	Exon 1 of 3	ENSP00000460841.2	I3L3Z2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447778 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720280

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32476

American (AMR) AF: 0.00 AC: 0 AN: 40534

Ashkenazi Jewish (ASJ) AF: 0.0000395 AC: 1 AN: 25338

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 84342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107266

Other (OTH) AF: 0.00 AC: 0 AN: 59778

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.61	T
PhyloP100		4.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.50		Loss of disorder (P = 0.013)
MVP		0.79
MPC		1.5
ClinPred		1.0	D
GERP RS		5.5
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.25

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

Other links and lift over

dbSNP: rs1246772868; hg19: chr17-7760726;