12-6943867-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NR_023317.1(RNU7-1):n.52C>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 0.0181 in 939,128 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (20 hom., cov: 33)
  • Exomes 𝑓: 0.019 (166 hom.)
• Consequence: RNU7-1 NR_023317.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.752

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-6943867-C-T is Benign according to our data. Variant chr12-6943867-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1301050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0154 (2344/152260) while in subpopulation AMR AF= 0.0223 (341/15294). AF 95% confidence interval is 0.0203. There are 20 homozygotes in gnomad4. There are 1077 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNU7-1	NR_023317.1	n.52C>T		non_coding_transcript_exon_variant	1/1
C12orf57	NM_001301834.1	c.-16+205C>T		intron_variant
C12orf57	NM_001301836.2	c.13+205C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNU7-1	ENST00000458811.1	n.52C>T		non_coding_transcript_exon_variant	1/1
	ENST00000607421.2	n.764G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2343 AN: 152142 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00956

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.00755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0186 AC: 14674 AN: 786868 Hom.: 166 Cov.: 10 AF XY: 0.0187 AC XY: 7373 AN XY: 394480

Gnomad4 AFR exome AF: 0.00838

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0299

Gnomad4 EAS exome AF: 0.000931

Gnomad4 SAS exome AF: 0.00909

Gnomad4 FIN exome AF: 0.00767

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.0170

GnomAD4 genome AF: 0.0154 AC: 2344 AN: 152260 Hom.: 20 Cov.: 33 AF XY: 0.0145 AC XY: 1077 AN XY: 74440

Gnomad4 AFR AF: 0.00953

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00644

Gnomad4 FIN AF: 0.00755

Gnomad4 NFE AF: 0.0191

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.00429 Hom.: 0

Bravo AF: 0.0164

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	-0.62
Cadd	Benign	0.058
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: rs149374821; hg19: chr12-7053030;