Genetic Variant C19orf12:c.*3402delT (chr19-29699309-TA-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_031448.6(C19orf12):c.*3402delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 334,830 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 0 hom. )

Consequence

C19orf12
NM_031448.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.50

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00439 (830/189278) while in subpopulation MID AF= 0.00612 (4/654). AF 95% confidence interval is 0.00411. There are 0 homozygotes in gnomad4_exome. There are 514 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C19orf12	NM_031448.6 link	c.*3402delT		3_prime_UTR_variant	Exon 3 of 3	ENST00000323670.14	NP_113636.2	Q9NSK7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C19orf12	ENST00000323670 link	c.*3402delT		3_prime_UTR_variant	Exon 3 of 3	2	NM_031448.6	ENSP00000313332.9		Q9NSK7-4

Frequencies

GnomAD3 genomes

AF:

0.000137

AC:

AN:

145474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000219

Gnomad FIN

AF:

0.000432

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000121

Gnomad OTH

AF:

0.000500

GnomAD4 exome

AF:

0.00439

AC:

830

AN:

189278

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

514

AN XY:

108898

show subpopulations

Gnomad4 AFR exome

AF:

0.00270

Gnomad4 AMR exome

AF:

0.00532

Gnomad4 ASJ exome

AF:

0.00650

Gnomad4 EAS exome

AF:

0.00205

Gnomad4 SAS exome

AF:

0.00459

Gnomad4 FIN exome

AF:

0.00415

Gnomad4 NFE exome

AF:

0.00441

Gnomad4 OTH exome

AF:

0.00357

GnomAD4 genome

AF:

0.000137

AC:

AN:

145552

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

AN XY:

70728

show subpopulations

Gnomad4 AFR

AF:

0.000127

Gnomad4 AMR

AF:

0.0000686

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000219

Gnomad4 FIN

AF:

0.000432

Gnomad4 NFE

AF:

0.000121

Gnomad4 OTH

AF:

0.000496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over