rs3214051

Positions:

• chr12-56725452-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000356769.7(NACA):​c.-192C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,198 control chromosomes in the GnomAD database, including 29,433 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (29406 hom., cov: 33)
  • Exomes 𝑓: 0.74 (27 hom.)
• Consequence: NACA ENST00000356769.7 5_prime_UTR
• Scores: Splicing: ADA: 0.00003699
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

Genes affected

NACA (HGNC:7629): (nascent polypeptide associated complex subunit alpha) This gene encodes a protein that associates with basic transcription factor 3 (BTF3) to form the nascent polypeptide-associated complex (NAC). This complex binds to nascent proteins that lack a signal peptide motif as they emerge from the ribosome, blocking interaction with the signal recognition particle (SRP) and preventing mistranslocation to the endoplasmic reticulum. This protein is an IgE autoantigen in atopic dermatitis patients. Alternative splicing results in multiple transcript variants, but the full length nature of some of these variants, including those encoding very large proteins, has not been determined. There are multiple pseudogenes of this gene on different chromosomes. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NACA	ENST00000356769.7	c.-192C>T		5_prime_UTR_variant	1/8	1		P4
NACA	ENST00000546392.6	c.-218C>T		5_prime_UTR_variant	1/8	2		P4
NACA	ENST00000549855.5	c.-192C>T		splice_region_variant, 5_prime_UTR_variant	2/6	5

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93808 AN: 151990 Hom.: 29400 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.744 AC: 67 AN: 90 Hom.: 27 Cov.: 0 AF XY: 0.703 AC XY: 45 AN XY: 64

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.617 AC: 93849 AN: 152108 Hom.: 29406 Cov.: 33 AF XY: 0.624 AC XY: 46402 AN XY: 74380

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.639

Alfa AF: 0.634 Hom.: 14540

Bravo AF: 0.609

Asia WGS AF: 0.738 AC: 2562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3214051; hg19: chr12-57119236;