dbSNP rs3214051: NACA:c.-192C>T (chr12-56725452-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Publications

18 publications found

Variant links:

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]

NACA links:

ENSG00000285625 (HGNC:):

ENSG00000285625 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NACA	NM_001365896.1 link	c.-192C>T		upstream_gene_variant		ENST00000454682.6	NP_001352825.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000285625	ENST00000647707.1 link	c.362-112C>T	intron_variant	Intron 4 of 6			ENSP00000497880.1	A0A3B3ITS8
NACA	ENST00000454682.6 link	c.-192C>T	upstream_gene_variant		5	NM_001365896.1	ENSP00000403817.1	E9PAV3-1
NACA	ENST00000547914.5 link	n.-192C>T	upstream_gene_variant		5		ENSP00000446745.1	F8W029

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93808

AN:

151990

Hom.:

29400

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.703

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.729

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.617

AC:

93849

AN:

152108

Hom.:

29406

Cov.:

AF XY:

0.624

AC XY:

46402

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.519

AC:

21528

AN:

41506

American (AMR)

AF:

0.681

AC:

10414

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1977

AN:

3472

East Asian (EAS)

AF:

0.733

AC:

3784

AN:

5162

South Asian (SAS)

AF:

0.745

AC:

3593

AN:

4820

European-Finnish (FIN)

AF:

0.708

AC:

7505

AN:

10594

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.630

AC:

42841

AN:

67950

Other (OTH)

AF:

0.639

AC:

1349

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1842

3684

5525

7367

9209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.634

Hom.:

25459

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

(source)

DANN

Benign

0.80

PhyloP100

0.14

PromoterAI

-0.030

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over