Variant rs199730337 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_138425.4(C12orf57):c.229+25_229+43del variant causes a splice donor 5th base, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,610,452 control chromosomes in the GnomAD database, including 1,090 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 386 hom., cov: 32)

Exomes 𝑓: 0.011 ( 704 hom. )

Consequence

C12orf57
NM_138425.4 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.05

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

BP6

Variant 12-6944654-TGGGTCAGACGCGGGAAGGC-T is Benign according to our data. Variant chr12-6944654-TGGGTCAGACGCGGGAAGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 466308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf57	NM_138425.4 linkuse as main transcript	c.229+25_229+43del		splice_donor_5th_base_variant, intron_variant		ENST00000229281.6	NP_612434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6 linkuse as main transcript	c.229+25_229+43del		splice_donor_5th_base_variant, intron_variant		1	NM_138425.4	ENSP00000229281	P1
	ENST00000607421.2 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0451

AC:

6856

AN:

151972

Hom.:

383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0884

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.00706

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00277

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0305

AC:

7625

AN:

250344

Hom.:

406

AF XY:

0.0235

AC XY:

3182

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.0214

Gnomad EAS exome

AF:

0.0315

Gnomad SAS exome

AF:

0.00663

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0112

AC:

16262

AN:

1458362

Hom.:

704

AF XY:

0.0101

AC XY:

7288

AN XY:

724718

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0346

Gnomad4 SAS exome

AF:

0.00750

Gnomad4 FIN exome

AF:

0.000188

Gnomad4 NFE exome

AF:

0.00295

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0453

AC:

6888

AN:

152090

Hom.:

386

Cov.:

AF XY:

0.0449

AC XY:

3338

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0887

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.0337

Gnomad4 SAS

AF:

0.00686

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00277

Gnomad4 OTH

AF:

0.0421

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0565

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00261

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Apr 14, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 07, 2021

- -

Temtamy syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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