12-6943738-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000607421.2(ENSG00000272173):n.892_893insT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,226,588 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (54 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (43 hom.)
• Consequence: ENST00000607421.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.155

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-6943738-G-GA is Benign according to our data. Variant chr12-6943738-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 1300798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0156 (2372/152290) while in subpopulation AFR AF= 0.0485 (2016/41550). AF 95% confidence interval is 0.0468. There are 54 homozygotes in gnomad4. There are 1157 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 54 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C12orf57	NM_001301834.1	c.-16+82dup		intron_variant
C12orf57	NM_001301836.2	c.13+82dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000607421.2	n.892_893insT		non_coding_transcript_exon_variant	1/1
C12orf57	ENST00000545581.5	c.-16+82dup		intron_variant		3
C12orf57	ENST00000538392.1	n.388+82dup		intron_variant, non_coding_transcript_variant		2
C12orf57	ENST00000542222.1	n.230+82dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2372 AN: 152172 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00207 AC: 2229 AN: 1074298 Hom.: 43 Cov.: 19 AF XY: 0.00200 AC XY: 1049 AN XY: 524248

Gnomad4 AFR exome AF: 0.0519

Gnomad4 AMR exome AF: 0.00619

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.0110

Gnomad4 SAS exome AF: 0.000198

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000689

Gnomad4 OTH exome AF: 0.00437

GnomAD4 genome AF: 0.0156 AC: 2372 AN: 152290 Hom.: 54 Cov.: 32 AF XY: 0.0155 AC XY: 1157 AN XY: 74474

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0125

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0170

Bravo AF: 0.0174

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 18, 2021

- -

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: rs369359232; hg19: chr12-7052901;