Genetic Variant C12orf57:c.-271C>T (chr12-6943851-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001301834.1(C12orf57):c.-16+189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 900,868 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.256

Variant links:

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]

C12orf57 links:

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

RNU7-1 links:

ENSG00000272173 (HGNC:):

ENSG00000272173 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 12-6943851-C-T is Benign according to our data. Variant chr12-6943851-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1301230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00556 (846/152258) while in subpopulation AFR AF= 0.0147 (610/41560). AF 95% confidence interval is 0.0137. There are 6 homozygotes in gnomad4. There are 390 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_138425.4 link	c.-271C>T		upstream_gene_variant		ENST00000229281.6	NP_612434.1	Q99622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6 link	c.-271C>T		upstream_gene_variant		1	NM_138425.4	ENSP00000229281.5		Q99622

Frequencies

GnomAD3 genomes

AF:

0.00555

AC:

845

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00430

GnomAD4 exome

AF:

0.00252

AC:

1884

AN:

748610

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

914

AN XY:

375634

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00189

Gnomad4 EAS exome

AF:

0.00176

Gnomad4 SAS exome

AF:

0.00175

Gnomad4 FIN exome

AF:

0.00111

Gnomad4 NFE exome

AF:

0.00239

Gnomad4 OTH exome

AF:

0.00271

GnomAD4 genome

AF:

0.00556

AC:

846

AN:

152258

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

390

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.00589

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RNU7-1: BS1, BS2 -

Mar 29, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.33

DANN

Benign

0.78

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over