Genetic Variant C12orf57:c.-16+83G>T (chr12-6943745-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001301834.1(C12orf57):c.-16+83G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,201,300 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 22 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.62

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-6943745-G-T is Benign according to our data. Variant chr12-6943745-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1300741.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (2171/151746) while in subpopulation AFR AF = 0.0499 (2068/41432). AF 95% confidence interval is 0.0481. There are 50 homozygotes in GnomAd4. There are 1023 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
C12orf57	NM_001301834.1 link	c.-16+83G>T	intron_variant	Intron 1 of 3	NP_001288763.1	Q99622
C12orf57	NM_001301836.2 link	c.13+83G>T	intron_variant	Intron 1 of 2	NP_001288765.1
RNU7-1	NR_023317.1 link	n.-71G>T	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
C12orf57	ENST00000545581.5 link	c.-16+83G>T	intron_variant	Intron 1 of 3	3	ENSP00000440602.1	Q99622
ENSG00000272173	ENST00000607421.2 link	n.886C>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
C12orf57	ENST00000538392.1 link	n.388+83G>T	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2164

AN:

151628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00473

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000886

Gnomad OTH

AF:

0.0120

GnomAD4 exome

AF:

0.00119

AC:

1250

AN:

1049554

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

532

AN XY:

512596

show subpopulations

Gnomad4 AFR exome

AF:

0.0516

AC:

1084

AN:

21028

Gnomad4 AMR exome

AF:

0.00201

AC:

AN:

16406

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

12692

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

13784

Gnomad4 SAS exome

AF:

0.000140

AC:

AN:

64114

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

11596

Gnomad4 NFE exome

AF:

0.0000242

AC:

AN:

867116

Gnomad4 Remaining exome

AF:

0.00249

AC:

AN:

38946

Heterozygous variant carriers

115

173

230

288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0143

AC:

2171

AN:

151746

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1023

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.0499

AC:

0.0499131

AN:

0.0499131

Gnomad4 AMR

AF:

0.00472

AC:

0.00472379

AN:

0.00472379

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000886

AC:

0.0000885949

AN:

0.0000885949

Gnomad4 OTH

AF:

0.0119

AC:

0.0118934

AN:

0.0118934

Heterozygous variant carriers

111

223

334

446

557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00289

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 13, 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

-0.82

CADD

Benign

0.0010

DANN

Benign

0.56

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