Variant 19-29699376-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_031448.6(C19orf12):c.*3336C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 375,822 control chromosomes in the GnomAD database, including 677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.059 ( 444 hom., cov: 30)

Exomes 𝑓: 0.036 ( 233 hom. )

Consequence

C19orf12
NM_031448.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02

Variant links:

Genes affected

C19orf12 (HGNC:25443): (chromosome 19 open reading frame 12) This gene encodes a small transmembrane protein. Mutations in this gene are a cause of neurodegeneration with brain iron accumulation-4 (NBIA4), but the specific function of the encoded protein is unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

C19orf12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 19-29699376-G-A is Benign according to our data. Variant chr19-29699376-G-A is described in ClinVar as [Benign]. Clinvar id is 328665.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C19orf12	NM_031448.6 linkuse as main transcript	c.*3336C>T		3_prime_UTR_variant	3/3	ENST00000323670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C19orf12	ENST00000323670.14 linkuse as main transcript	c.*3336C>T		3_prime_UTR_variant	3/3	2	NM_031448.6	P1	Q9NSK7-4

Frequencies

GnomAD3 genomes

AF:

0.0588

AC:

8916

AN:

151548

Hom.:

441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.0822

Gnomad SAS

AF:

0.0554

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0600

GnomAD3 exomes

AF:

0.0458

AC:

3336

AN:

72770

Hom.:

120

AF XY:

0.0453

AC XY:

1827

AN XY:

40300

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0290

Gnomad ASJ exome

AF:

0.0685

Gnomad EAS exome

AF:

0.0777

Gnomad SAS exome

AF:

0.0532

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0382

GnomAD4 exome

AF:

0.0359

AC:

8051

AN:

224160

Hom.:

233

Cov.:

AF XY:

0.0368

AC XY:

4717

AN XY:

128170

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.0287

Gnomad4 ASJ exome

AF:

0.0713

Gnomad4 EAS exome

AF:

0.0788

Gnomad4 SAS exome

AF:

0.0485

Gnomad4 FIN exome

AF:

0.0168

Gnomad4 NFE exome

AF:

0.0244

Gnomad4 OTH exome

AF:

0.0433

GnomAD4 genome

AF:

0.0590

AC:

8945

AN:

151662

Hom.:

444

Cov.:

AF XY:

0.0586

AC XY:

4347

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.0382

Gnomad4 ASJ

AF:

0.0741

Gnomad4 EAS

AF:

0.0824

Gnomad4 SAS

AF:

0.0555

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0636

Alfa

AF:

0.0426

Hom.:

Bravo

AF:

0.0621

Asia WGS

AF:

0.0940

AC:

326

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodegeneration with brain iron accumulation 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.28

DANN

Benign

0.83

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