Genetic Variant ENST00000323670:c.*3745G>C (chr19-29698967-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000323670.14(C19orf12):c.*3745G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 450,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

C19orf12
ENST00000323670.14 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodegeneration with brain iron accumulation 4
Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Illumina
hereditary spastic paraplegia 43
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

C19orf12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000323670.14. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C19orf12	NM_031448.6	MANE Select	c.*3745G>C	3_prime_UTR	Exon 3 of 3	NP_113636.2	Q9NSK7-4
C19orf12	NM_001256047.2		c.*3745G>C	3_prime_UTR	Exon 3 of 3	NP_001242976.1	Q9NSK7-4
C19orf12	NM_001256046.3		c.*3792G>C	3_prime_UTR	Exon 4 of 4	NP_001242975.1	Q9NSK7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf12	ENST00000323670.14	TSL:2 MANE Select	c.*3745G>C		3_prime_UTR	Exon 3 of 3	ENSP00000313332.9	Q9NSK7-4
	C19orf12	ENST00000890432.1		c.*3745G>C		downstream_gene	N/A	ENSP00000560491.1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000784

AC:

AN:

127556

AF XY:

0.0000143

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000266

AC:

AN:

301086

Hom.:

Cov.:

AF XY:

0.0000350

AC XY:

AN XY:

171640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8538

American (AMR)

AF:

0.00

AC:

AN:

27234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10772

East Asian (EAS)

AF:

0.00

AC:

AN:

9180

South Asian (SAS)

AF:

0.00

AC:

AN:

59512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1146

European-Non Finnish (NFE)

AF:

0.0000505

AC:

AN:

158334

Other (OTH)

AF:

0.00

AC:

AN:

14020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40536

American (AMR)

AF:

0.00

AC:

AN:

14856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5056

South Asian (SAS)

AF:

0.00

AC:

AN:

4702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67476

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.0

(source)

DANN

Benign

0.38

PhyloP100

-0.087

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over