12-6944550-G-C

Variant names:

• chr12-6944550-G-C
• NM_138425.4:c.127G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138425.4(C12orf57):​c.127G>C​(p.Ala43Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,782 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C12orf57 NM_138425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.84

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]

ENSG00000272173 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_138425.4	c.127G>C	p.Ala43Pro	missense_variant	Exon 2 of 3	ENST00000229281.6	NP_612434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6	c.127G>C	p.Ala43Pro	missense_variant	Exon 2 of 3	1	NM_138425.4	ENSP00000229281.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D;D;D;D;D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.90	.;D;D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	1.8	L;.;.;L;.
PROVEAN	Uncertain	-2.8	D;.;D;D;.
REVEL	Uncertain	0.57
Sift	Uncertain	0.0070	D;.;D;D;.
Sift4G	Uncertain	0.020	D;D;D;D;D
Polyphen		1.0	D;.;D;D;.
Vest4		0.90, 0.93, 0.94, 0.90
MutPred		0.35		Gain of catalytic residue at A43 (P = 3e-04);Gain of catalytic residue at A43 (P = 3e-04);Gain of catalytic residue at A43 (P = 3e-04);Gain of catalytic residue at A43 (P = 3e-04);.;
MVP		0.97
MPC		0.71
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.92
gMVP		0.95

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-7053713;