chr19-29706248-C-T

Variant names:

• chr19-29706248-C-T
• rs3746314
• NM_031448.6:c.160+2006G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031448.6(C19orf12):​c.160+2006G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,266 control chromosomes in the GnomAD database, including 1,678 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1678 hom., cov: 33)
• Consequence: C19orf12 NM_031448.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• neurodegeneration with brain iron accumulation 4

  Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Illumina, Ambry Genetics, G2P
• hereditary spastic paraplegia 43

  Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031448.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf12	NM_031448.6	MANE Select	c.160+2006G>A		intron	N/A	NP_113636.2
	C19orf12	NM_001031726.4		c.160+2006G>A		intron	N/A	NP_001026896.3
	C19orf12	NM_001256047.2		c.160+2006G>A		intron	N/A	NP_001242976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf12	ENST00000323670.14	TSL:2 MANE Select	c.160+2006G>A		intron	N/A	ENSP00000313332.9
	C19orf12	ENST00000592153.5	TSL:1	c.160+2006G>A		intron	N/A	ENSP00000467117.1
	C19orf12	ENST00000591243.1	TSL:1	c.160+2006G>A		intron	N/A	ENSP00000467516.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20479 AN: 152148 Hom.: 1673 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20506 AN: 152266 Hom.: 1678 Cov.: 33 AF XY: 0.142 AC XY: 10547 AN XY: 74438

African (AFR) AF: 0.111 AC: 4624 AN: 41552

American (AMR) AF: 0.208 AC: 3182 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3472

East Asian (EAS) AF: 0.370 AC: 1913 AN: 5174

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4828

European-Finnish (FIN) AF: 0.157 AC: 1662 AN: 10590

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7344 AN: 68034

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.118 Hom.: 5069

Bravo AF: 0.137

Asia WGS AF: 0.283 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.31
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3746314; hg19: chr19-30197155;