Genetic Variant ENST00000544681.1:c.-263C>T (chr12-6943859-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000544681.1(C12orf57):c.-263C>T variant causes a 5 prime UTR 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
ENST00000544681.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.26

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

Aicardi-Goutieres syndrome 9
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia

RNU7-1 links:

ENSG00000272173 (HGNC:):

ENSG00000272173 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000544681.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf57	NM_001301834.1	c.-16+197C>T	intron	N/A	NP_001288763.1	Q99622
C12orf57	NM_001301836.2	c.13+197C>T	intron	N/A	NP_001288765.1
RNU7-1	NR_023317.1	n.44C>T	non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf57	ENST00000544681.1	TSL:2	c.-263C>T	5_prime_UTR	Exon 1 of 2	ENSP00000475422.1	U3KQ07
C12orf57	ENST00000537087.5	TSL:2	c.-263C>T	5_prime_UTR	Exon 1 of 3	ENSP00000440937.1	F5GXW5
C12orf57	ENST00000921170.1		c.-263C>T	5_prime_UTR	Exon 1 of 2	ENSP00000591229.1

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67611

AN:

151960

Hom.:

18563

Cov.:

show subpopulations

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.:

AF XY:

0.320

AC XY:

125680

AN XY:

392818

show subpopulations

African (AFR)

AF:

0.814

AC:

14611

AN:

17946

American (AMR)

AF:

0.369

AC:

6163

AN:

16690

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

4493

AN:

14248

East Asian (EAS)

AF:

0.275

AC:

7443

AN:

27060

South Asian (SAS)

AF:

0.339

AC:

17703

AN:

52176

European-Finnish (FIN)

AF:

0.250

AC:

5429

AN:

21686

Middle Eastern (MID)

AF:

0.465

AC:

1188

AN:

2554

European-Non Finnish (NFE)

AF:

0.305

AC:

181970

AN:

597144

Other (OTH)

AF:

0.350

AC:

12301

AN:

35124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

8115

16230

24345

32460

40575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5438

10876

16314

21752

27190

<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:

0.445

AC:

67721

AN:

152078

Hom.:

18616

Cov.:

AF XY:

0.438

AC XY:

32551

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.787

AC:

32659

AN:

41472

American (AMR)

AF:

0.403

AC:

6151

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1040

AN:

3470

East Asian (EAS)

AF:

0.268

AC:

1387

AN:

5170

South Asian (SAS)

AF:

0.330

AC:

1591

AN:

4820

European-Finnish (FIN)

AF:

0.246

AC:

2605

AN:

10588

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.306

AC:

20792

AN:

67962

Other (OTH)

AF:

0.456

AC:

964

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1588

3176

4763

6351

7939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.485

Hom.:

4997

Bravo

AF:

0.472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.30

(source)

DANN

Benign

0.61

PhyloP100

-1.3

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over