Genetic Variant NM_138425.4:c.229+25_229+43dupTCAGACGCGGGAAGGCGGG (chr12-6944654-T-TGGGTCAGACGCGGGAAGGC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_138425.4(C12orf57):c.229+25_229+43dupTCAGACGCGGGAAGGCGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,610,468 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

C12orf57
NM_138425.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.58

Publications

3 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 Gene-Disease associations (from GenCC):

temtamy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

C12orf57 links:

ENSG00000272173 (HGNC:):

ENSG00000272173 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
C12orf57	NM_138425.4	MANE Select	c.229+25_229+43dupTCAGACGCGGGAAGGCGGG	intron	N/A	NP_612434.1
C12orf57	NM_001301834.1		c.229+25_229+43dupTCAGACGCGGGAAGGCGGG	intron	N/A	NP_001288763.1
C12orf57	NM_001301836.2		c.190+25_190+43dupTCAGACGCGGGAAGGCGGG	intron	N/A	NP_001288765.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
C12orf57	ENST00000229281.6	TSL:1 MANE Select	c.229+25_229+43dupTCAGACGCGGGAAGGCGGG		intron	N/A	ENSP00000229281.5
C12orf57	ENST00000544681.1	TSL:2	c.254_272dupTCAGACGCGGGAAGGCGGG	p.Val92GlnfsTer34	frameshift	Exon 2 of 2	ENSP00000475422.1
C12orf57	ENST00000538392.1	TSL:2	n.590_608dupTCAGACGCGGGAAGGCGGG		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

250344

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1458442

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724750

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33394

American (AMR)

AF:

0.000179

AC:

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.0000758

AC:

AN:

39588

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53118

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1109368

Other (OTH)

AF:

0.0000498

AC:

AN:

60234

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

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:

0.0000329

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41392

American (AMR)

AF:

0.000197

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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

PhyloP100

2.6

Mutation Taster

=52/148

disease causing

(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