dbSNP rs76168000: C12orf57:c.-16+149C>A (chr12-6943811-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001301834.1(C12orf57):c.-16+149C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 858,010 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.23

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:

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 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

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	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf57	NM_001301834.1		c.-16+149C>A	intron	N/A	NP_001288763.1	Q99622
C12orf57	NM_001301836.2		c.13+149C>A	intron	N/A	NP_001288765.1
C12orf57	NM_138425.4	MANE Select	c.-311C>A	upstream_gene	N/A	NP_612434.1	Q99622

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf57	ENST00000852280.1		c.-16+149C>A	intron	N/A	ENSP00000522339.1
C12orf57	ENST00000545581.5	TSL:3	c.-16+149C>A	intron	N/A	ENSP00000440602.1	Q99622
ENSG00000272173	ENST00000607421.3	TSL:6	n.913G>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000170

AC:

AN:

705798

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

353760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15864

American (AMR)

AF:

0.00

AC:

AN:

14480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11606

East Asian (EAS)

AF:

0.00

AC:

AN:

19332

South Asian (SAS)

AF:

0.0000389

AC:

AN:

51432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2266

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

546292

Other (OTH)

AF:

0.0000664

AC:

AN:

30118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

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:

0.0000197

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0020

(source)

DANN

Benign

0.52

PhyloP100

-3.2

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=99/1

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