dbSNP rs781842057: C12orf57:c.-277A>G (chr12-6943845-A-G) – ACMG Classification: Likely_pathogenic (7 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 8P and 1B. PP5_Very_StrongBP4

The NM_001301834.1(C12orf57):c.-16+183A>G variant causes a intron change. The variant allele was found at a frequency of 0.0000682 in 893,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Clinical Significance

Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 4.38

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PP5

Variant 12-6943845-A-G is Pathogenic according to our data. Variant chr12-6943845-A-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1328524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301834.1. 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+183A>G	intron	N/A	NP_001288763.1	Q99622
C12orf57	NM_001301836.2	c.13+183A>G	intron	N/A	NP_001288765.1
RNU7-1	NR_023317.1	n.30A>G	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.-277A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000475422.1	U3KQ07
C12orf57	ENST00000537087.5	TSL:2	c.-277A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000440937.1	F5GXW5
C12orf57	ENST00000921170.1		c.-277A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000591229.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000742

AC:

AN:

741664

Hom.:

Cov.:

AF XY:

0.0000833

AC XY:

AN XY:

372056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16934

American (AMR)

AF:

0.00

AC:

AN:

16196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13414

East Asian (EAS)

AF:

0.000120

AC:

AN:

25060

South Asian (SAS)

AF:

0.0000389

AC:

AN:

51436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19630

Middle Eastern (MID)

AF:

0.000827

AC:

AN:

2418

European-Non Finnish (NFE)

AF:

0.0000834

AC:

AN:

563552

Other (OTH)

AF:

0.0000303

AC:

AN:

33024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000416

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aicardi-Goutieres syndrome 9 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

4.4

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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