12-6943859-C-A

Variant names:

• chr12-6943859-C-A
• rs7965269
• ENST00000544681.1:c.-263C>A

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+197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 786,956 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: 33)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 16 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]

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

ENSG00000272173 (HGNC:):

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=-0.61).

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+197C>A		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+197C>A		intron	N/A	NP_001288765.1
	RNU7-1	NR_023317.1		n.44C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000544681.1	TSL:2	c.-263C>A		5_prime_UTR	Exon 1 of 2	ENSP00000475422.1	U3KQ07
	C12orf57	ENST00000537087.5	TSL:2	c.-263C>A		5_prime_UTR	Exon 1 of 3	ENSP00000440937.1	F5GXW5
	C12orf57	ENST00000921170.1		c.-263C>A		5_prime_UTR	Exon 1 of 2	ENSP00000591229.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000127 AC: 1 AN: 786956 Hom.: 0 Cov.: 10 AF XY: 0.00000254 AC XY: 1 AN XY: 393956

African (AFR) AF: 0.00 AC: 0 AN: 17986

American (AMR) AF: 0.00 AC: 0 AN: 16734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14286

East Asian (EAS) AF: 0.00 AC: 0 AN: 27130

South Asian (SAS) AF: 0.00 AC: 0 AN: 52232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2562

European-Non Finnish (NFE) AF: 0.00000167 AC: 1 AN: 599090

Other (OTH) AF: 0.00 AC: 0 AN: 35210

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4997

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.16
DANN	Benign	0.55
PhyloP100		-1.3
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

Splicing

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

Other links and lift over

dbSNP: rs7965269; hg19: chr12-7053022;