Variant chr19-29699340-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_031448.6(C19orf12):c.*3372C>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 0.0115 in 365,318 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 30)

Exomes 𝑓: 0.012 ( 28 hom. )

Consequence

C19orf12
NM_031448.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.364

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 19-29699340-G-A is Benign according to our data. Variant chr19-29699340-G-A is described in ClinVar as [Benign]. Clinvar id is 328663.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1593/151802) while in subpopulation NFE AF= 0.0172 (1168/67914). AF 95% confidence interval is 0.0164. There are 13 homozygotes in gnomad4. There are 716 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C19orf12	NM_031448.6 linkuse as main transcript	c.*3372C>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.*3372C>T		3_prime_UTR_variant	3/3	2	NM_031448.6	P1	Q9NSK7-4

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1595

AN:

151684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.00782

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0106

AC:

693

AN:

65640

Hom.:

AF XY:

0.0107

AC XY:

386

AN XY:

36022

show subpopulations

Gnomad AFR exome

AF:

0.00336

Gnomad AMR exome

AF:

0.00974

Gnomad ASJ exome

AF:

0.00728

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00204

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.0178

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0122

AC:

2600

AN:

213516

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

1385

AN XY:

122160

show subpopulations

Gnomad4 AFR exome

AF:

0.00418

Gnomad4 AMR exome

AF:

0.00898

Gnomad4 ASJ exome

AF:

0.00520

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0105

AC:

1593

AN:

151802

Hom.:

Cov.:

AF XY:

0.00965

AC XY:

716

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.00340

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00168

Gnomad4 FIN

AF:

0.00782

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.00173

AC:

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

-1.0

CADD

Benign

0.094

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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