rs199730337

chr12-6944654-TGGGTCAGACGCGGGAAGGC-Tchr12-6944654-TGGGTCAGACGCGGGAAGGC-TGGGTCAGACGCGGGAAGGCGGGTCAGACGCGGGAAGGC

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 8.05

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]

(HGNC:):

ACMG classification

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	UniProt
C12orf57	NM_138425.4	c.229+25_229+43del		splice_donor_5th_base_variant, intron_variant		ENST00000229281.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6856 AN: 151972 Hom.: 383 Cov.: 32

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

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

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.: 32 AF XY: 0.0449 AC XY: 3338 AN XY: 74346

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.: 9

Bravo AF: 0.0565

Asia WGS AF: 0.0230 AC: 81 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

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199730337; hg19: chr12-7053817;