17-7857225-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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)
• Consequence: NAA38 NM_032356.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096304476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA38	NM_001320925.4	c.82-27T>A		intron_variant	Intron 1 of 2	ENST00000575771.6	NP_001307854.1
NAA38	NM_032356.6	c.199T>A	p.Ser67Thr	missense_variant	Exon 1 of 2		NP_115732.2
NAA38	NM_001320924.3	c.82-27T>A		intron_variant	Intron 1 of 2		NP_001307853.1
NAA38	NM_001330111.2	c.4-27T>A		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.82-27T>A		intron_variant	Intron 1 of 2	1	NM_001320925.4	ENSP00000460172.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.199T>A (p.S67T) alteration is located in exon 1 (coding exon 1) of the NAA38 gene. This alteration results from a T to A substitution at nucleotide position 199, causing the serine (S) at amino acid position 67 to be replaced by a threonine (T). 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	-0.29	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
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
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7760543;