chr19-29699309-T-TA

Position:

• chr19-29699309-T-TA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031448.6(C19orf12):​c.*3402_*3403insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 336,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000096 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: C19orf12 NM_031448.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C19orf12	NM_031448.6	c.*3402_*3403insT		3_prime_UTR_variant	3/3	ENST00000323670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C19orf12	ENST00000323670.14	c.*3402_*3403insT		3_prime_UTR_variant	3/3	2	NM_031448.6	P1

Frequencies

GnomAD3 genomes AF: 0.0000962 AC: 14 AN: 145498 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000206

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000219

Gnomad FIN AF: 0.000108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000755

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00227 AC: 434 AN: 191334 Hom.: 0 Cov.: 0 AF XY: 0.00224 AC XY: 247 AN XY: 110126

Gnomad4 AFR exome AF: 0.00247

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.00248

Gnomad4 EAS exome AF: 0.000581

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.00187

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.0000962 AC: 14 AN: 145576 Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 8 AN XY: 70742

Gnomad4 AFR AF: 0.0000762

Gnomad4 AMR AF: 0.000206

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000219

Gnomad4 FIN AF: 0.000108

Gnomad4 NFE AF: 0.0000755

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodegeneration with brain iron accumulation 4 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs139713991; hg19: chr19-30190216;