12-6943864-T-C

Variant summary

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

The NR_023317.1(RNU7-1):n.49T>C 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 0.00193 in 937,242 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (3 hom.)
• Consequence: RNU7-1 NR_023317.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.89

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-6943864-T-C is Benign according to our data. Variant chr12-6943864-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3024660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNU7-1	NR_023317.1	n.49T>C		non_coding_transcript_exon_variant	1/1
C12orf57	NM_001301834.1	c.-16+202T>C		intron_variant
C12orf57	NM_001301836.2	c.13+202T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNU7-1	ENST00000458811.1	n.49T>C		non_coding_transcript_exon_variant	1/1
	ENST00000607421.2	n.767A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 536 AN: 152224 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00695

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00247

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00162 AC: 1272 AN: 784900 Hom.: 3 Cov.: 10 AF XY: 0.00153 AC XY: 602 AN XY: 393746

Gnomad4 AFR exome AF: 0.00543

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00284

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000574

Gnomad4 FIN exome AF: 0.000177

Gnomad4 NFE exome AF: 0.00174

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152342 Hom.: 2 Cov.: 33 AF XY: 0.00336 AC XY: 250 AN XY: 74492

Gnomad4 AFR AF: 0.00693

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.00247

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.00356

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

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

RNU7-1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.0010
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: rs145994149; hg19: chr12-7053027;