rs139938808

Variant names:

• chr12-6944509-C-G
• NM_138425.4:c.86C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-6944509-C-G
• chr12-6944509-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138425.4(C12orf57):​c.86C>G​(p.Ala29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign 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: 3.43

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29215264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_138425.4	c.86C>G	p.Ala29Gly	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.86C>G	p.Ala29Gly	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: 1461018 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726814

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T;T;T;T
Eigen	Benign	-0.0021
Eigen_PC	Benign	0.072
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.85	.;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.1	L;.;.;L
PROVEAN	Benign	-1.9	N;.;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.20	T;.;D;T
Sift4G	Benign	0.42	T;T;T;T
Polyphen		0.10	B;.;P;B
Vest4		0.22, 0.41, 0.34
MutPred		0.22		Gain of catalytic residue at A29 (P = 0.0111);Gain of catalytic residue at A29 (P = 0.0111);Gain of catalytic residue at A29 (P = 0.0111);Gain of catalytic residue at A29 (P = 0.0111);
MVP		0.84
MPC		0.23
ClinPred		0.67	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.46

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: chr12-7053672;