12-56718260-T-G

Position:

• chr12-56718260-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001365896.1(NACA):​c.3270A>C​(p.Pro1090Pro) 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 0.00033 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NACA NM_001365896.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.89

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]

ENSG00000285625 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-56718260-T-G is Benign according to our data. Variant chr12-56718260-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NACA	NM_001365896.1	c.3270A>C	p.Pro1090Pro	synonymous_variant	3/9	ENST00000454682.6	NP_001352825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NACA	ENST00000454682.6	c.3270A>C	p.Pro1090Pro	synonymous_variant	3/9	5	NM_001365896.1	ENSP00000403817.1
ENSG00000285625	ENST00000647707.1	c.512-3573A>C		intron_variant				ENSP00000497880.1
NACA	ENST00000547914.5	n.71-3573A>C		intron_variant		5		ENSP00000446745.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 35 AN: 104148 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.000301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000620

Gnomad SAS AF: 0.000981

Gnomad FIN AF: 0.000800

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000364 AC: 35 AN: 962060 Hom.: 0 Cov.: 49 AF XY: 0.0000309 AC XY: 14 AN XY: 452852

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000109

Gnomad4 EAS exome AF: 0.0000635

Gnomad4 SAS exome AF: 0.0000408

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000351

Gnomad4 OTH exome AF: 0.0000885

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000326 AC: 34 AN: 104174 Hom.: 0 Cov.: 23 AF XY: 0.000411 AC XY: 21 AN XY: 51036

Gnomad4 AFR AF: 0.000263

Gnomad4 AMR AF: 0.000294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000621

Gnomad4 SAS AF: 0.000986

Gnomad4 FIN AF: 0.000800

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

NACA: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs768199123; hg19: chr12-57112044;