12-6943745-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000607421.2(ENSG00000272173):n.886C>A 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 0.00285 in 1,201,300 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (22 hom.)
• Consequence: ENST00000607421.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.62

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-6943745-G-T is Benign according to our data. Variant chr12-6943745-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1300741.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2171/151746) while in subpopulation AFR AF= 0.0499 (2068/41432). AF 95% confidence interval is 0.0481. There are 50 homozygotes in gnomad4. There are 1023 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C12orf57	NM_001301834.1	c.-16+83G>T		intron_variant
C12orf57	NM_001301836.2	c.13+83G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000607421.2	n.886C>A		non_coding_transcript_exon_variant	1/1
C12orf57	ENST00000545581.5	c.-16+83G>T		intron_variant		3
C12orf57	ENST00000538392.1	n.388+83G>T		intron_variant, non_coding_transcript_variant		2
C12orf57	ENST00000542222.1	n.230+83G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2164 AN: 151628 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00473

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: 0.0000886

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00119 AC: 1250 AN: 1049554 Hom.: 22 Cov.: 17 AF XY: 0.00104 AC XY: 532 AN XY: 512596

Gnomad4 AFR exome AF: 0.0516

Gnomad4 AMR exome AF: 0.00201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000242

Gnomad4 OTH exome AF: 0.00249

GnomAD4 genome AF: 0.0143 AC: 2171 AN: 151746 Hom.: 50 Cov.: 32 AF XY: 0.0138 AC XY: 1023 AN XY: 74230

Gnomad4 AFR AF: 0.0499

Gnomad4 AMR AF: 0.00472

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000886

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.0110 Hom.: 9

Bravo AF: 0.0160

Asia WGS AF: 0.00289 AC: 10 AN: 3474

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 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.0010
Dann	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs114309358; hg19: chr12-7052908;