12-6943866-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NR_023317.1(RNU7-1):n.51C>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 0.0038 in 934,242 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (4 hom.)
• Consequence: RNU7-1 NR_023317.1 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:2
• Conservation: PhyloP100: 0.538

Genes affected

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

(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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 12-6943866-C-T is Benign according to our data. Variant chr12-6943866-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1202613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNU7-1	NR_023317.1	n.51C>T		non_coding_transcript_exon_variant	1/1
C12orf57	NM_001301834.1	c.-16+204C>T		intron_variant
C12orf57	NM_001301836.2	c.13+204C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNU7-1	ENST00000458811.1	n.51C>T		non_coding_transcript_exon_variant	1/1
	ENST00000607421.2	n.765G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00545 AC: 830 AN: 152182 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00347 AC: 2711 AN: 781944 Hom.: 4 Cov.: 10 AF XY: 0.00335 AC XY: 1313 AN XY: 391962

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.00272

Gnomad4 ASJ exome AF: 0.00456

Gnomad4 EAS exome AF: 0.00253

Gnomad4 SAS exome AF: 0.000707

Gnomad4 FIN exome AF: 0.000444

Gnomad4 NFE exome AF: 0.00355

Gnomad4 OTH exome AF: 0.00408

GnomAD4 genome AF: 0.00551 AC: 839 AN: 152298 Hom.: 5 Cov.: 33 AF XY: 0.00526 AC XY: 392 AN XY: 74474

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00323

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000160 Hom.: 0

Bravo AF: 0.00641

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	C12orf57: BS1, BS2; RNU7-1: BS1, BS2 -

Aicardi-Goutieres syndrome 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	1.2
Dann	Benign	0.70
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: rs139594532; hg19: chr12-7053029;