12-6943732-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000607421.2(ENSG00000272173):n.899C>T 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 0.000669 in 1,242,512 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (2 hom.)
• Consequence: ENST00000607421.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0330

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-6943732-G-A is Benign according to our data. Variant chr12-6943732-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1301045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C12orf57	NM_001301834.1	c.-16+70G>A		intron_variant
C12orf57	NM_001301836.2	c.13+70G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000607421.2	n.899C>T		non_coding_transcript_exon_variant	1/1
C12orf57	ENST00000545581.5	c.-16+70G>A		intron_variant		3
C12orf57	ENST00000538392.1	n.388+70G>A		intron_variant, non_coding_transcript_variant		2
C12orf57	ENST00000542222.1	n.230+70G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 469 AN: 151920 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.00

Gnomad OTH AF: 0.00288

GnomAD4 exome AF: 0.000330 AC: 360 AN: 1090474 Hom.: 2 Cov.: 21 AF XY: 0.000271 AC XY: 144 AN XY: 532244

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.000353

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000444

Gnomad4 OTH exome AF: 0.000550

GnomAD4 genome AF: 0.00310 AC: 471 AN: 152038 Hom.: 4 Cov.: 32 AF XY: 0.00311 AC XY: 231 AN XY: 74334

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00354

Asia WGS AF: 0.00115 AC: 5 AN: 3478

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

Mar 29, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.52
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73262861; hg19: chr12-7052895;