NM_138425.4:c.86_87delCCinsGT

Variant names:

• chr12-6944509-CC-GT
• NM_138425.4:c.86_87delCCinsGT
• C12orf57 p.Ala29Gly

Variant summary

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

The NM_138425.4(C12orf57):​c.86_87delCCinsGT​(p.Ala29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A29V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C12orf57 NM_138425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43
• Publications: 0 publications found

Genes affected

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 Gene-Disease associations (from GenCC):

• temtamy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ENSG00000272173 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138425.4. 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
	C12orf57	NM_138425.4	MANE Select	c.86_87delCCinsGT	p.Ala29Gly	missense	N/A	NP_612434.1	Q99622
	C12orf57	NM_001301834.1		c.86_87delCCinsGT	p.Ala29Gly	missense	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.47_48delCCinsGT	p.Ala16Gly	missense	N/A	NP_001288765.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000229281.6	TSL:1 MANE Select	c.86_87delCCinsGT	p.Ala29Gly	missense	N/A	ENSP00000229281.5	Q99622
	C12orf57	ENST00000852280.1		c.86_87delCCinsGT	p.Ala29Gly	missense	N/A	ENSP00000522339.1
	C12orf57	ENST00000545581.5	TSL:3	c.86_87delCCinsGT	p.Ala29Gly	missense	N/A	ENSP00000440602.1	Q99622

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-7053672;