12-6943813-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000607421.2(ENSG00000272173):n.818G>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 0.00113 in 865,876 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 0.0039 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (5 hom.)
• Consequence: ENST00000607421.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21

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]

RNU7-1 (HGNC:34033): (RNA, U7 small nuclear 1) Implicated in Aicardi-Goutieres syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-6943813-C-T is Benign according to our data. Variant chr12-6943813-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1300813.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C12orf57	NM_001301834.1	c.-16+151C>T		intron_variant
C12orf57	NM_001301836.2	c.13+151C>T		intron_variant
RNU7-1	NR_023317.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000607421.2	n.818G>A		non_coding_transcript_exon_variant	1/1
RNU7-1	ENST00000458811.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 601 AN: 152256 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000530 AC: 378 AN: 713502 Hom.: 5 Cov.: 9 AF XY: 0.000501 AC XY: 179 AN XY: 357410

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.000545

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000352

Gnomad4 SAS exome AF: 0.000272

Gnomad4 FIN exome AF: 0.0000673

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.000951

GnomAD4 genome AF: 0.00394 AC: 601 AN: 152374 Hom.: 1 Cov.: 33 AF XY: 0.00365 AC XY: 272 AN XY: 74524

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.00482

Asia WGS AF: 0.00202 AC: 7 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

Apr 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.0020
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142699589; hg19: chr12-7052976;