chr12-6944167-G-T

Position:

• chr12-6944167-G-T

Variant summary

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

The NM_138425.4(C12orf57):​c.46G>T​(p.Ala16Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C12orf57 NM_138425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf57	NM_138425.4	c.46G>T	p.Ala16Ser	missense_variant	1/3	ENST00000229281.6	NP_612434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6	c.46G>T	p.Ala16Ser	missense_variant	1/3	1	NM_138425.4	ENSP00000229281.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251436 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461856 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	D;T;T;D
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	.;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.9	L;.;.;L
PROVEAN	Benign	-2.0	N;.;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.041	D;.;D;D
Sift4G	Uncertain	0.039	D;D;D;D
Polyphen		0.79	P;.;.;P
Vest4		0.60, 0.61, 0.61
MutPred		0.19		Gain of glycosylation at A16 (P = 0.0054);Gain of glycosylation at A16 (P = 0.0054);Gain of glycosylation at A16 (P = 0.0054);Gain of glycosylation at A16 (P = 0.0054);
MVP		0.87
MPC		0.28
ClinPred		0.89	D
GERP RS		3.9
Varity_R		0.22
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs782651043; hg19: chr12-7053330;