Variant 12-6943856-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001301834.1(C12orf57):c.-16+194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 932,388 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 3 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.951

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 12-6943856-T-C is Benign according to our data. Variant chr12-6943856-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2578675.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000263 (40/152270) while in subpopulation SAS AF= 0.00373 (18/4822). AF 95% confidence interval is 0.00241. There are 1 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
C12orf57	NM_001301834.1 link	c.-16+194T>C	intron_variant		NP_001288763.1	Q99622
C12orf57	NM_001301836.2 link	c.13+194T>C	intron_variant		NP_001288765.1
RNU7-1	NR_023317.1 link	n.41T>C	non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
C12orf57	ENST00000544681 link	c.-266T>C	5_prime_UTR_variant	1/2	2	ENSP00000475422.1	U3KQ07
C12orf57	ENST00000537087 link	c.-266T>C	5_prime_UTR_variant	1/3	2	ENSP00000440937.1	F5GXW5
C12orf57	ENST00000545581.5 link	c.-16+194T>C	intron_variant		3	ENSP00000440602.1	Q99622

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000341

AC:

266

AN:

780118

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

184

AN XY:

390774

show subpopulations

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:

0.00306

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.000487

GnomAD4 genome

AF:

0.000263

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

RNU7-1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.046

DANN

Benign

0.71

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.3

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