12-6943811-C-T

Variant names:

• chr12-6943811-C-T
• rs76168000
• NM_001301834.1:c.-16+149C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001301834.1(C12orf57):​c.-16+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 858,098 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (86 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (45 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.23

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 12-6943811-C-T is Benign according to our data. Variant chr12-6943811-C-T is described in ClinVar as [Benign]. Clinvar id is 1266944.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_138425.4	c.-311C>T		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.-311C>T		upstream_gene_variant		1	NM_138425.4	ENSP00000229281.5

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2815 AN: 152206 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00283 AC: 1994 AN: 705774 Hom.: 45 Cov.: 9 AF XY: 0.00298 AC XY: 1055 AN XY: 353744

Gnomad4 AFR exome AF: 0.0607

Gnomad4 AMR exome AF: 0.00622

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.000139

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.00395

GnomAD4 genome AF: 0.0185 AC: 2812 AN: 152324 Hom.: 86 Cov.: 33 AF XY: 0.0183 AC XY: 1363 AN XY: 74494

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.00751

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.000499 Hom.: 1

Bravo AF: 0.0203

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 28, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0020
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76168000; hg19: chr12-7052974;