chr17-7857225-A-T

Variant names:

• chr17-7857225-A-T
• rs923486015
• ENST00000333775.9:c.199T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032356.6(NAA38):​c.199T>A​(p.Ser67Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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)
• Consequence: NAA38 NM_032356.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• 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=0.096304476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032356.6. 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.82-27T>A		intron	N/A	NP_001307854.1	Q9BRA0-1
	NAA38	NM_032356.6		c.199T>A	p.Ser67Thr	missense	Exon 1 of 2	NP_115732.2
	NAA38	NM_001320924.3		c.82-27T>A		intron	N/A	NP_001307853.1	I3L3Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA38	ENST00000333775.9	TSL:1	c.199T>A	p.Ser67Thr	missense	Exon 1 of 2	ENSP00000332103.5	Q9BRA0-2
	NAA38	ENST00000575771.6	TSL:1 MANE Select	c.82-27T>A		intron	N/A	ENSP00000460172.2	Q9BRA0-1
	NAA38	ENST00000576384.1	TSL:2	c.-102T>A		5_prime_UTR	Exon 1 of 2	ENSP00000460085.1	I3L310

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.9
DANN	Benign	0.88
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.073
Sift	Uncertain	0.013	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.22		Gain of helix (P = 0.027)
MVP		0.17
MPC		0.50
ClinPred		0.32	T
GERP RS		-2.0
PromoterAI		0.0034	Neutral
gMVP		0.17

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: rs923486015; hg19: chr17-7760543;