NM_138425.4:c.30C>G

Variant names:

• chr12-6944151-C-G
• rs199643110
• NM_138425.4:c.30C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_138425.4(C12orf57):​c.30C>G​(p.Ala10Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A10A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: C12orf57 NM_138425.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.892
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 12-6944151-C-G is Benign according to our data. Variant chr12-6944151-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1681814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.892 with no splicing effect.

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.30C>G	p.Ala10Ala	synonymous	Exon 1 of 3	NP_612434.1	Q99622
	C12orf57	NM_001301834.1		c.30C>G	p.Ala10Ala	synonymous	Exon 2 of 4	NP_001288763.1	Q99622
	C12orf57	NM_001301837.2		c.30C>G	p.Ala10Ala	synonymous	Exon 1 of 3	NP_001288766.1	F5GXW5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000229281.6	TSL:1 MANE Select	c.30C>G	p.Ala10Ala	synonymous	Exon 1 of 3	ENSP00000229281.5	Q99622
	C12orf57	ENST00000852280.1		c.30C>G	p.Ala10Ala	synonymous	Exon 3 of 5	ENSP00000522339.1
	C12orf57	ENST00000545581.5	TSL:3	c.30C>G	p.Ala10Ala	synonymous	Exon 2 of 4	ENSP00000440602.1	Q99622

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Temtamy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.89
PromoterAI		-0.096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs199643110; hg19: chr12-7053314;