4-139378633-C-T

Variant names:

• chr4-139378633-C-T
• rs3762865
• NM_057175.5:c.2057-123C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_057175.5(NAA15):​c.2057-123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 451,152 control chromosomes in the GnomAD database, including 10,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4398 hom., cov: 32)
  • Exomes 𝑓: 0.19 (6258 hom.)
• Consequence: NAA15 NM_057175.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39
• Publications: 6 publications found

Genes affected

NAA15 (HGNC:30782): (N-alpha-acetyltransferase 15, NatA auxiliary subunit) N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes the auxillary subunit of the N-terminal acetyltransferase A (NatA) complex. [provided by RefSeq, Jan 2017]

NAA15 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 50

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 4-139378633-C-T is Benign according to our data. Variant chr4-139378633-C-T is described in ClinVar as Benign. ClinVar VariationId is 1229201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA15	NM_057175.5	c.2057-123C>T		intron_variant	Intron 16 of 19	ENST00000296543.10	NP_476516.1
NAA15	NM_001410842.1	c.2057-123C>T		intron_variant	Intron 16 of 19		NP_001397771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA15	ENST00000296543.10	c.2057-123C>T		intron_variant	Intron 16 of 19	1	NM_057175.5	ENSP00000296543.4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34576 AN: 151922 Hom.: 4391 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.195 AC: 58185 AN: 299112 Hom.: 6258 AF XY: 0.197 AC XY: 30385 AN XY: 153982

African (AFR) AF: 0.329 AC: 2495 AN: 7594

American (AMR) AF: 0.130 AC: 1080 AN: 8322

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 2428 AN: 9914

East Asian (EAS) AF: 0.269 AC: 6213 AN: 23080

South Asian (SAS) AF: 0.373 AC: 3910 AN: 10482

European-Finnish (FIN) AF: 0.194 AC: 5322 AN: 27484

Middle Eastern (MID) AF: 0.247 AC: 361 AN: 1464

European-Non Finnish (NFE) AF: 0.170 AC: 32643 AN: 192306

Other (OTH) AF: 0.202 AC: 3733 AN: 18466

GnomAD4 genome AF: 0.228 AC: 34601 AN: 152040 Hom.: 4398 Cov.: 32 AF XY: 0.227 AC XY: 16874 AN XY: 74306

African (AFR) AF: 0.328 AC: 13610 AN: 41454

American (AMR) AF: 0.152 AC: 2328 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1348 AN: 5188

South Asian (SAS) AF: 0.394 AC: 1903 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2107 AN: 10560

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11672 AN: 67952

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.201 Hom.: 751

Bravo AF: 0.224

Asia WGS AF: 0.301 AC: 1049 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.72
DANN	Benign	0.71
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs3762865; hg19: chr4-140299787;