12-6943851-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.36C>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 0.00303 in 900,868 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: RNU7-1 NR_023317.1 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.256

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=-0.59).
• BP6: Variant 12-6943851-C-T is Benign according to our data. Variant chr12-6943851-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1301230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNU7-1	NR_023317.1	n.36C>T		non_coding_transcript_exon_variant	1/1
C12orf57	NM_001301834.1	c.-16+189C>T		intron_variant
C12orf57	NM_001301836.2	c.13+189C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNU7-1	ENST00000458811.1	n.36C>T		non_coding_transcript_exon_variant	1/1
	ENST00000607421.2	n.780G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 845 AN: 152140 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00252 AC: 1884 AN: 748610 Hom.: 9 Cov.: 10 AF XY: 0.00243 AC XY: 914 AN XY: 375634

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.00189

Gnomad4 EAS exome AF: 0.00176

Gnomad4 SAS exome AF: 0.00175

Gnomad4 FIN exome AF: 0.00111

Gnomad4 NFE exome AF: 0.00239

Gnomad4 OTH exome AF: 0.00271

GnomAD4 genome AF: 0.00556 AC: 846 AN: 152258 Hom.: 6 Cov.: 33 AF XY: 0.00524 AC XY: 390 AN XY: 74466

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.000210 Hom.: 0

Bravo AF: 0.00589

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	RNU7-1: BS1, BS2 -
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	-0.59
Cadd	Benign	0.33
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116861153; hg19: chr12-7053014;