Variant chr12-6944473-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1

The NM_138425.4(C12orf57):c.53-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000127 in 1,611,438 control chromosomes in the GnomAD database, including 1 homozygotes. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

C12orf57
NM_138425.4 splice_region, intron

Scores

Splicing: ADA: 0.9935

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.08

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 12-6944473-C-T is Benign according to our data. Variant chr12-6944473-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 466310.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000256 (39/152390) while in subpopulation AMR AF= 0.00222 (34/15308). AF 95% confidence interval is 0.00163. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf57	NM_138425.4 linkuse as main transcript	c.53-3C>T		splice_region_variant, intron_variant		ENST00000229281.6	NP_612434.1	Q99622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6 linkuse as main transcript	c.53-3C>T		splice_region_variant, intron_variant		1	NM_138425.4	ENSP00000229281.5		Q99622

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

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:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000352

AC:

AN:

247104

Hom.:

AF XY:

0.000276

AC XY:

AN XY:

134058

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.000828

GnomAD4 exome

AF:

0.000114

AC:

166

AN:

1459048

Hom.:

Cov.:

AF XY:

0.0000951

AC XY:

AN XY:

725748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000711

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000256

AC:

AN:

152390

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000128

Hom.:

Bravo

AF:

0.000253

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2024

In silico analysis indicates that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge -

Temtamy syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.64

SpliceAI score (max)

0.040

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