Variant 12-6943656-GACTT-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000607421.2(ENSG00000272173):n.971_974del variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

ENST00000607421.2 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.544

Variant links:

Genes affected

(HGNC:):

links:

C12orf57 (HGNC:29521): (chromosome 12 open reading frame 57) This gene is ubiquitously expressed in human tissues. It is required for development of the human corpus callosum. Mutations in this gene are associated with Temtamy syndrome (TEMTYS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

C12orf57 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
C12orf57	NM_001301836.2 linkuse as main transcript	c.9_12del	p.Asp3GlufsTer7	frameshift_variant, splice_region_variant	1/3
C12orf57	NM_001301834.1 linkuse as main transcript	c.-20_-17del		splice_region_variant, 5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
	ENST00000607421.2 linkuse as main transcript	n.971_974del	non_coding_transcript_exon_variant	1/1
C12orf57	ENST00000545581.5 linkuse as main transcript	c.-20_-17del	splice_region_variant, 5_prime_UTR_variant	1/4	3
C12orf57	ENST00000538392.1 linkuse as main transcript	n.384_387del	splice_region_variant, non_coding_transcript_exon_variant	2/3	2
C12orf57	ENST00000542222.1 linkuse as main transcript	n.226_229del	splice_region_variant, non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

C12orf57-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 2024

The C12orf57 c.9_12delCTTA variant is predicted to result in a frameshift and premature protein termination (p.Asp3Glufs*7). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Loss-of-function has not been established as a disease mechanism for this gene, and therefore the clinical significance of this variant is currently uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.