12-64390457-C-A

Variant names:

• chr12-64390457-C-A
• rs374898623
• NM_001170633.2:c.109G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001170633.2(C12orf56):​c.109G>T​(p.Glu37*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000686 in 1,457,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C12orf56 NM_001170633.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84
• Publications: 0 publications found

Genes affected

C12orf56 (HGNC:26967): (chromosome 12 open reading frame 56)

ENSG00000293269 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170633.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf56	NM_001170633.2	MANE Select	c.109G>T	p.Glu37*	stop_gained	Exon 1 of 13	NP_001164104.1	Q8IXR9-1
	C12orf56	NM_001099676.3		c.109G>T	p.Glu37*	stop_gained	Exon 1 of 11	NP_001093146.1	Q8IXR9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf56	ENST00000543942.7	TSL:5 MANE Select	c.109G>T	p.Glu37*	stop_gained	Exon 1 of 13	ENSP00000446101.2	Q8IXR9-1
	C12orf56	ENST00000333722.9	TSL:1	c.109G>T	p.Glu37*	stop_gained	Exon 1 of 11	ENSP00000329698.5	Q8IXR9-2
	ENSG00000293269	ENST00000482431.5	TSL:1	n.467+1043C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457216 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725158

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111678

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.43
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		4.8
Vest4		0.17
GERP RS		3.7
PromoterAI		-0.012	Neutral
Mutation Taster		=30/170	disease causing (fs/PTC)

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: rs374898623; hg19: chr12-64784237;