chr12-6943859-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001301834.1(C12orf57):​c.-16+197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 936,706 control chromosomes in the GnomAD database, including 62,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (18616 hom., cov: 33)
  • Exomes 𝑓: 0.32 (43405 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.26

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-6943859-C-T is Benign according to our data. Variant chr12-6943859-C-T is described in ClinVar as [Benign]. Clinvar id is 1181108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_138425.4	c.-263C>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.-263C>T		upstream_gene_variant		1	NM_138425.4	ENSP00000229281.5

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67611 AN: 151960 Hom.: 18563 Cov.: 33

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.320 AC: 251301 AN: 784628 Hom.: 43405 Cov.: 10 AF XY: 0.320 AC XY: 125680 AN XY: 392818

Gnomad4 AFR exome AF: 0.814

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.445 AC: 67721 AN: 152078 Hom.: 18616 Cov.: 33 AF XY: 0.438 AC XY: 32551 AN XY: 74358

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.456

Alfa AF: 0.239 Hom.: 807

Bravo AF: 0.472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.30
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7965269; hg19: chr12-7053022; COSMIC: COSV57547057; COSMIC: COSV57547057;