Variant 12-56718533-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001365896.1(NACA):c.2997T>C(p.Gly999Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0096 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00050 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NACA
NM_001365896.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0730

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 12-56718533-A-G is Benign according to our data. Variant chr12-56718533-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3239091.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.073 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NACA	NM_001365896.1 linkuse as main transcript	c.2997T>C	p.Gly999Gly	synonymous_variant	3/9	ENST00000454682.6	NP_001352825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NACA	ENST00000454682.6 linkuse as main transcript	c.2997T>C	p.Gly999Gly	synonymous_variant	3/9	5	NM_001365896.1	ENSP00000403817.1	E9PAV3-1
ENSG00000285625	ENST00000647707.1 linkuse as main transcript	c.512-3846T>C		intron_variant				ENSP00000497880.1	A0A3B3ITS8
NACA	ENST00000547914.5 linkuse as main transcript	n.71-3846T>C		intron_variant		5		ENSP00000446745.1	F8W029

Frequencies

GnomAD3 genomes

AF:

0.00960

AC:

299

AN:

31150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00793

Gnomad AMI

AF:

0.00909

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.00968

Gnomad EAS

AF:

0.00611

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00898

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00885

GnomAD3 exomes

AF:

0.0000723

AC:

AN:

124478

Hom.:

AF XY:

0.0000439

AC XY:

AN XY:

68300

show subpopulations

Gnomad AFR exome

AF:

0.000106

Gnomad AMR exome

AF:

0.000237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000102

Gnomad SAS exome

AF:

0.000296

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000161

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000503

AC:

499

AN:

991238

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

295

AN XY:

474492

show subpopulations

Gnomad4 AFR exome

AF:

0.000102

Gnomad4 AMR exome

AF:

0.000223

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.00364

Gnomad4 FIN exome

AF:

0.000927

Gnomad4 NFE exome

AF:

0.000346

Gnomad4 OTH exome

AF:

0.000585

GnomAD4 genome

AF:

0.00959

AC:

299

AN:

31194

Hom.:

Cov.:

AF XY:

0.00812

AC XY:

123

AN XY:

15142

show subpopulations

Gnomad4 AFR

AF:

0.00790

Gnomad4 AMR

AF:

0.00697

Gnomad4 ASJ

AF:

0.00968

Gnomad4 EAS

AF:

0.00611

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.00898

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.00870

Alfa

AF:

0.000633

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

NACA: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.95

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over