Variant chr12-6943843-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4

The NR_023317.1(RNU7-1):n.28C>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.000652 in 888,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 0 hom. )

Consequence

RNU7-1
NR_023317.1 non_coding_transcript_exon

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

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

RNU7-1 links:

(HGNC:):

links:

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]

C12orf57 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 12-6943843-C-T is Pathogenic according to our data. Variant chr12-6943843-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1202611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
RNU7-1	NR_023317.1 linkuse as main transcript	n.28C>T	non_coding_transcript_exon_variant	1/1
C12orf57	NM_001301834.1 linkuse as main transcript	c.-16+181C>T	intron_variant
C12orf57	NM_001301836.2 linkuse as main transcript	c.13+181C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNU7-1	ENST00000458811.1 linkuse as main transcript	n.28C>T		non_coding_transcript_exon_variant	1/1
	ENST00000607421.2 linkuse as main transcript	n.788G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.000956

GnomAD4 exome

AF:

0.000659

AC:

485

AN:

736138

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

245

AN XY:

369452

show subpopulations

Gnomad4 AFR exome

AF:

0.000590

Gnomad4 AMR exome

AF:

0.000745

Gnomad4 ASJ exome

AF:

0.000149

Gnomad4 EAS exome

AF:

0.000321

Gnomad4 SAS exome

AF:

0.000370

Gnomad4 FIN exome

AF:

0.000258

Gnomad4 NFE exome

AF:

0.000734

Gnomad4 OTH exome

AF:

0.000548

GnomAD4 genome

AF:

0.000617

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000106

Hom.:

Bravo

AF:

0.000593

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Aicardi-Goutieres syndrome 9

Pathogenic:3

Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Sep 02, 2022	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 16, 2021	- -
Pathogenic, no assertion criteria provided	clinical testing	Undiagnosed Diseases Network, NIH	Sep 06, 2022	- -

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Oct 26, 2022

Published functional studies demonstrate a damaging effect with severely reduced processing efficiency (Kolev and Steitz, 2006); This variant is associated with the following publications: (PMID: 33230297, 16547514) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.89

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over