12-6943732-G-C

Variant names:

• chr12-6943732-G-C
• rs73262861
• NM_001301834.1:c.-16+70G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001301834.1(C12orf57):​c.-16+70G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000917 in 1,090,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• 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]

ENSG00000272173 (HGNC:):

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

RNU7-1 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301834.1. 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_001301834.1		c.-16+70G>C		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+70G>C		intron	N/A	NP_001288765.1
	RNU7-1	NR_023317.1		n.-84G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000852280.1		c.-16+70G>C		intron	N/A	ENSP00000522339.1
	C12orf57	ENST00000545581.5	TSL:3	c.-16+70G>C		intron	N/A	ENSP00000440602.1	Q99622
	ENSG00000272173	ENST00000607421.3	TSL:6	n.992C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.17e-7 AC: 1 AN: 1090484 Hom.: 0 Cov.: 21 AF XY: 0.00000188 AC XY: 1 AN XY: 532246

African (AFR) AF: 0.00 AC: 0 AN: 22404

American (AMR) AF: 0.00 AC: 0 AN: 17004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13318

East Asian (EAS) AF: 0.00 AC: 0 AN: 13534

South Asian (SAS) AF: 0.00 AC: 0 AN: 67220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4098

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 901108

Other (OTH) AF: 0.00 AC: 0 AN: 40004

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.40
DANN	Benign	0.49
PhyloP100		0.033
PromoterAI		-0.092	Neutral

Splicing

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

Other links and lift over

dbSNP: rs73262861; hg19: chr12-7052895;