Genetic Variant C12orf57:c.-16+82dupA (chr12-6943738-G-GA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001301834.1(C12orf57):c.-16+82dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,226,588 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.016 ( 54 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 43 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.155

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:

ENSG00000272173 (HGNC:):

ENSG00000272173 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-6943738-G-GA is Benign according to our data. Variant chr12-6943738-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 1300798.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0156 (2372/152290) while in subpopulation AFR AF= 0.0485 (2016/41550). AF 95% confidence interval is 0.0468. There are 54 homozygotes in gnomad4. There are 1157 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
C12orf57	NM_001301834.1 link	c.-16+82dupA	intron_variant	Intron 1 of 3	NP_001288763.1	Q99622
C12orf57	NM_001301836.2 link	c.13+82dupA	intron_variant	Intron 1 of 2	NP_001288765.1
RNU7-1	NR_023317.1 link	n.-78_-77insA	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
C12orf57	ENST00000545581.5 link	c.-16+82dupA	intron_variant	Intron 1 of 3	3	ENSP00000440602.1	Q99622
ENSG00000272173	ENST00000607421.2 link	n.892dupT	non_coding_transcript_exon_variant	Exon 1 of 1	6
C12orf57	ENST00000538392.1 link	n.388+82dupA	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2372

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0125

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.00207

AC:

2229

AN:

1074298

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1049

AN XY:

524248

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.00619

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0110

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000689

Gnomad4 OTH exome

AF:

0.00437

GnomAD4 genome

AF:

0.0156

AC:

2372

AN:

152290

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1157

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0485

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0125

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.0170

Bravo

AF:

0.0174

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 18, 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

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