Genetic Variant C12orf57:c.-255C>G (chr12-6943867-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001301834.1(C12orf57):c.-16+205C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 939,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.752

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

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+205C>G	intron	N/A	NP_001288763.1	Q99622
C12orf57	NM_001301836.2	c.13+205C>G	intron	N/A	NP_001288765.1
RNU7-1	NR_023317.1	n.52C>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.-255C>G	5_prime_UTR	Exon 1 of 2	ENSP00000475422.1	U3KQ07
C12orf57	ENST00000537087.5	TSL:2	c.-255C>G	5_prime_UTR	Exon 1 of 3	ENSP00000440937.1	F5GXW5
C12orf57	ENST00000921170.1		c.-255C>G	5_prime_UTR	Exon 1 of 2	ENSP00000591229.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000889

AC:

AN:

787096

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

394590

show subpopulations

African (AFR)

AF:

0.0000566

AC:

AN:

17656

American (AMR)

AF:

0.000236

AC:

AN:

16964

Ashkenazi Jewish (ASJ)

AF:

0.0000687

AC:

AN:

14564

East Asian (EAS)

AF:

0.000215

AC:

AN:

27920

South Asian (SAS)

AF:

0.000496

AC:

AN:

52390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2584

European-Non Finnish (NFE)

AF:

0.0000469

AC:

AN:

596718

Other (OTH)

AF:

0.000113

AC:

AN:

35496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000112

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41560

American (AMR)

AF:

0.000458

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.040

(source)

DANN

Benign

0.67

PhyloP100

-0.75

PromoterAI

-0.064

Neutral

(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