rs781901992

Positions:

• chr12-6944186-CTAGTCAAGGCATAGGCTGCTGGCCTGGGG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_138425.4(C12orf57):​c.52+26_52+54del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,066 control chromosomes in the GnomAD database, including 172 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 33)
  • Exomes 𝑓: 0.014 (160 hom.)
• Consequence: C12orf57 NM_138425.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.27

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 -16 ACMG points.

• BP6: Variant 12-6944186-CTAGTCAAGGCATAGGCTGCTGGCCTGGGG-C is Benign according to our data. Variant chr12-6944186-CTAGTCAAGGCATAGGCTGCTGGCCTGGGG-C is described in ClinVar as [Likely_benign]. Clinvar id is 210549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0103 (1569/152272) while in subpopulation NFE AF= 0.0155 (1054/68002). AF 95% confidence interval is 0.0147. There are 12 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf57	NM_138425.4	c.52+26_52+54del		intron_variant		ENST00000229281.6	NP_612434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000229281.6	c.52+26_52+54del		intron_variant		1	NM_138425.4	ENSP00000229281	P1
	ENST00000607421.2	n.416_444del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1569 AN: 152154 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0114 AC: 2874 AN: 251392 Hom.: 21 AF XY: 0.0121 AC XY: 1648 AN XY: 135876

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00506

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.00598

Gnomad SAS exome AF: 0.0143

Gnomad FIN exome AF: 0.00430

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.0142 AC: 20701 AN: 1460794 Hom.: 160 AF XY: 0.0142 AC XY: 10292 AN XY: 726724

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.00508

Gnomad4 ASJ exome AF: 0.0217

Gnomad4 EAS exome AF: 0.00899

Gnomad4 SAS exome AF: 0.0133

Gnomad4 FIN exome AF: 0.00449

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0103 AC: 1569 AN: 152272 Hom.: 12 Cov.: 33 AF XY: 0.00991 AC XY: 738 AN XY: 74478

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.0132

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0115 Hom.: 2

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 29, 2015

- -

Temtamy syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 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: rs781901992; hg19: chr12-7053349;