12-6943869-G-A

Variant names:

• chr12-6943869-G-A
• rs782223539
• ENST00000537087:c.-253G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001301834.1(C12orf57):​c.-16+207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 953,356 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96

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]

RNU7-1 (HGNC:34033): (RNA, U7 small nuclear 1) Implicated in Aicardi-Goutieres syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272173 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_138425.4	c.-253G>A		upstream_gene_variant		ENST00000229281.6	NP_612434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6	c.-253G>A		upstream_gene_variant		1	NM_138425.4	ENSP00000229281.5

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152154 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000120 AC: 96 AN: 801202 Hom.: 1 Cov.: 10 AF XY: 0.000127 AC XY: 51 AN XY: 401514

Gnomad4 AFR exome AF: 0.000278

Gnomad4 AMR exome AF: 0.000232

Gnomad4 ASJ exome AF: 0.0000678

Gnomad4 EAS exome AF: 0.0000703

Gnomad4 SAS exome AF: 0.000493

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000872

Gnomad4 OTH exome AF: 0.000111

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152154 Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16 AN XY: 74324

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.000110

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 05, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 35320431) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs782223539; hg19: chr12-7053032;