chr12-6943845-A-T

Variant names:

• chr12-6943845-A-T
• rs781842057
• ENST00000544681:c.-277A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001301834.1(C12orf57):​c.-16+183A>T variant causes a intron change. The variant allele was found at a frequency of 0.0000027 in 741,662 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: 0.0000027 (0 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_001301834.1	c.-16+183A>T		intron_variant	Intron 1 of 3		NP_001288763.1
C12orf57	NM_001301836.2	c.13+183A>T		intron_variant	Intron 1 of 2		NP_001288765.1
RNU7-1	NR_023317.1	n.30A>T		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000544681	c.-277A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	2		ENSP00000475422.1
C12orf57	ENST00000537087	c.-277A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	2		ENSP00000440937.1
C12orf57	ENST00000544681	c.-277A>T		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000475422.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000270 AC: 2 AN: 741662 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 372056

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: 0.00000355

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.85
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

Publications

LitVar

Other links and lift over

dbSNP: rs781842057; hg19: chr12-7053008;