Variant chr19-29699194-G-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.*3518C>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 0.077 in 453,732 control chromosomes in the GnomAD database, including 2,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.058 ( 393 hom., cov: 31)

Exomes 𝑓: 0.086 ( 1627 hom. )

Consequence

C19orf12
NM_031448.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.359

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=-1.05).

BP6

Variant 19-29699194-G-T is Benign according to our data. Variant chr19-29699194-G-T is described in ClinVar as [Benign]. Clinvar id is 328657.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 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.*3518C>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.*3518C>A		3_prime_UTR_variant	3/3	2	NM_031448.6	P1	Q9NSK7-4

Frequencies

GnomAD3 genomes

AF:

0.0582

AC:

8833

AN:

151880

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0370

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0879

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0695

Gnomad OTH

AF:

0.0503

GnomAD3 exomes

AF:

0.0848

AC:

10850

AN:

127982

Hom.:

706

AF XY:

0.0931

AC XY:

6526

AN XY:

70090

show subpopulations

Gnomad AFR exome

AF:

0.00904

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0392

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.0886

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.0637

GnomAD4 exome

AF:

0.0865

AC:

26092

AN:

301734

Hom.:

1627

Cov.:

AF XY:

0.0966

AC XY:

16618

AN XY:

171964

show subpopulations

Gnomad4 AFR exome

AF:

0.00959

Gnomad4 AMR exome

AF:

0.0282

Gnomad4 ASJ exome

AF:

0.0405

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.0860

Gnomad4 NFE exome

AF:

0.0665

Gnomad4 OTH exome

AF:

0.0752

GnomAD4 genome

AF:

0.0581

AC:

8830

AN:

151998

Hom.:

393

Cov.:

AF XY:

0.0620

AC XY:

4608

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.0369

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.0879

Gnomad4 NFE

AF:

0.0695

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0465

Hom.:

Bravo

AF:

0.0482

Asia WGS

AF:

0.178

AC:

617

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 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

-1.1

CADD

Benign

0.35

DANN

Benign

0.39

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