Genetic Variant NM_138425.4:c.229+93C>G (chr12-6944745-C-G) – 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_138425.4(C12orf57):c.229+93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,574,406 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

C12orf57
NM_138425.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0460

Publications

10 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:

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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=-0.7).

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+93C>G	intron	N/A	NP_612434.1
C12orf57	NM_001301834.1		c.229+93C>G	intron	N/A	NP_001288763.1
C12orf57	NM_001301836.2		c.190+93C>G	intron	N/A	NP_001288765.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
C12orf57	ENST00000229281.6	TSL:1 MANE Select	c.229+93C>G	intron	N/A	ENSP00000229281.5
C12orf57	ENST00000544681.1	TSL:2	c.*10C>G	3_prime_UTR	Exon 2 of 2	ENSP00000475422.1
C12orf57	ENST00000852280.1		c.229+93C>G	intron	N/A	ENSP00000522339.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32794

American (AMR)

AF:

0.00

AC:

AN:

42614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24336

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38860

South Asian (SAS)

AF:

0.00

AC:

AN:

82820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086402

Other (OTH)

AF:

0.00

AC:

AN:

58466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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.:

3325

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.8

(source)

DANN

Benign

0.53

PhyloP100

0.046

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over