chr12-6943875-C-T

Position:

• chr12-6943875-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000537087(C12orf57):​c.-247C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 974,422 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (24 hom.)
• Consequence: C12orf57 ENST00000537087 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.51

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]

RNU7-1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 12-6943875-C-T is Benign according to our data. Variant chr12-6943875-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1301145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00876 (1334/152252) while in subpopulation AFR AF= 0.018 (747/41552). AF 95% confidence interval is 0.0169. There are 7 homozygotes in gnomad4. There are 620 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf57	NM_001301834.1	c.-16+213C>T		intron_variant			NP_001288763.1
C12orf57	NM_001301836.2	c.13+213C>T		intron_variant			NP_001288765.1
RNU7-1	NR_023317.1	n.60C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000537087	c.-247C>T		5_prime_UTR_variant	1/3	2		ENSP00000440937.1
C12orf57	ENST00000544681	c.-247C>T		5_prime_UTR_variant	1/2	2		ENSP00000475422.1
C12orf57	ENST00000545581.5	c.-16+213C>T		intron_variant		3		ENSP00000440602.1

Frequencies

GnomAD3 genomes AF: 0.00876 AC: 1333 AN: 152130 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.00523 AC: 4302 AN: 822170 Hom.: 24 Cov.: 11 AF XY: 0.00531 AC XY: 2186 AN XY: 411622

Gnomad4 AFR exome AF: 0.0166

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.00633

Gnomad4 EAS exome AF: 0.00645

Gnomad4 SAS exome AF: 0.00732

Gnomad4 FIN exome AF: 0.00119

Gnomad4 NFE exome AF: 0.00479

Gnomad4 OTH exome AF: 0.00578

GnomAD4 genome AF: 0.00876 AC: 1334 AN: 152252 Hom.: 7 Cov.: 33 AF XY: 0.00833 AC XY: 620 AN XY: 74444

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00656

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.000943

Gnomad4 NFE AF: 0.00550

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00414 Hom.: 2

Bravo AF: 0.00976

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.72
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115355876; hg19: chr12-7053038;