Genetic Variant NM_138425.4:c.229+93C>T (chr12-6944745-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138425.4(C12orf57):c.229+93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,574,308 control chromosomes in the GnomAD database, including 20,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1750 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18721 hom. )

Consequence

C12orf57
NM_138425.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0460

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 12-6944745-C-T is Benign according to our data. Variant chr12-6944745-C-T is described in ClinVar as [Benign]. Clinvar id is 1264683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_138425.4 link	c.229+93C>T		intron_variant	Intron 2 of 2	ENST00000229281.6	NP_612434.1	Q99622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6 link	c.229+93C>T		intron_variant	Intron 2 of 2	1	NM_138425.4	ENSP00000229281.5		Q99622

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19312

AN:

152050

Hom.:

1745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0305

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.190

AC:

40873

AN:

214620

Hom.:

5116

AF XY:

0.180

AC XY:

21184

AN XY:

117898

show subpopulations

Gnomad AFR exome

AF:

0.0270

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.219

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.153

AC:

217040

AN:

1422140

Hom.:

18721

Cov.:

AF XY:

0.152

AC XY:

106581

AN XY:

700970

show subpopulations

Gnomad4 AFR exome

AF:

0.0227

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.127

AC:

19326

AN:

152168

Hom.:

1750

Cov.:

AF XY:

0.132

AC XY:

9812

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0304

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.136

Hom.:

2103

Bravo

AF:

0.132

Asia WGS

AF:

0.221

AC:

766

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.7

DANN

Benign

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over