Variant 19-29699249-C-T 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.*3463G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 450,000 control chromosomes in the GnomAD database, including 3,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 2486 hom., cov: 30)

Exomes 𝑓: 0.077 ( 1250 hom. )

Consequence

C19orf12
NM_031448.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42

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=-1.04).

BP6

Variant 19-29699249-C-T is Benign according to our data. Variant chr19-29699249-C-T is described in ClinVar as [Benign]. Clinvar id is 328659.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 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.*3463G>A		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.*3463G>A		3_prime_UTR_variant	3/3	2	NM_031448.6	P1	Q9NSK7-4

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21198

AN:

151492

Hom.:

2480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0790

Gnomad ASJ

AF:

0.0987

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.0579

Gnomad FIN

AF:

0.0715

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0725

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.0781

AC:

9877

AN:

126400

Hom.:

657

AF XY:

0.0755

AC XY:

5224

AN XY:

69202

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.0499

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.0340

Gnomad SAS exome

AF:

0.0641

Gnomad FIN exome

AF:

0.0724

Gnomad NFE exome

AF:

0.0726

Gnomad OTH exome

AF:

0.0766

GnomAD4 exome

AF:

0.0769

AC:

22932

AN:

298390

Hom.:

1250

Cov.:

AF XY:

0.0739

AC XY:

12551

AN XY:

169842

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.0497

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.0324

Gnomad4 SAS exome

AF:

0.0631

Gnomad4 FIN exome

AF:

0.0702

Gnomad4 NFE exome

AF:

0.0737

Gnomad4 OTH exome

AF:

0.0866

GnomAD4 genome

AF:

0.140

AC:

21223

AN:

151610

Hom.:

2486

Cov.:

AF XY:

0.135

AC XY:

10012

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.0788

Gnomad4 ASJ

AF:

0.0987

Gnomad4 EAS

AF:

0.0346

Gnomad4 SAS

AF:

0.0578

Gnomad4 FIN

AF:

0.0715

Gnomad4 NFE

AF:

0.0725

Gnomad4 OTH

AF:

0.0987

Alfa

AF:

0.0499

Hom.:

Bravo

AF:

0.150

Asia WGS

AF:

0.0790

AC:

274

AN:

3478

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 12, 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

1.4

DANN

Benign

0.57

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