Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP5BP4

The ENST00000580972.2(RNU4ATAC):n.50G>A variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 700,228 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

RNU4ATAC
ENST00000580972.2 non_coding_transcript_exon

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:8U:1

Conservation

PhyloP100: 7.57

Publications

2 publications found

Variant links:

Genes affected

RNU4ATAC (HGNC:34016): (RNA, U4atac small nuclear) The small nuclear RNA (snRNA) encoded by this gene is part of the U12-dependent minor spliceosome complex. In addition to the encoded RNA, this ribonucleoprotein complex consists of U11, U12, U5, and U6atac snRNAs. The U12-dependent spliceosome acts on approximately 700 specific introns in the human genome. Defects in this gene are a cause of microcephalic osteodysplastic primordial dwarfism type 1 (MOPD). [provided by RefSeq, Jul 2011]

RNU4ATAC links:

CLASP1 (HGNC:17088): (cytoplasmic linker associated protein 1) CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]

CLASP1 links:

CLASP1-AS1 (HGNC:55328): (CLASP1 antisense RNA 1)

CLASP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP5

Variant 2-121530929-G-A is Pathogenic according to our data. Variant chr2-121530929-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 30184.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000580972.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNU4ATAC	NR_023343.3	MANE Select	n.50G>A	non_coding_transcript_exon	Exon 1 of 1
CLASP1	NM_001395891.1	MANE Select	c.196-604C>T	intron	N/A	NP_001382820.1
CLASP1	NM_015282.3		c.196-604C>T	intron	N/A	NP_056097.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.50G>A	non_coding_transcript_exon	Exon 1 of 1
CLASP1	ENST00000696935.1	MANE Select	c.196-604C>T	intron	N/A	ENSP00000512981.1
CLASP1	ENST00000263710.8	TSL:5	c.196-604C>T	intron	N/A	ENSP00000263710.4

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000123

AC:

AN:

130504

AF XY:

0.0000983

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000192

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

AN:

548048

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

296756

show subpopulations

African (AFR)

AF:

0.000191

AC:

AN:

15734

American (AMR)

AF:

0.000231

AC:

AN:

34706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20026

East Asian (EAS)

AF:

0.000218

AC:

AN:

32110

South Asian (SAS)

AF:

0.0000638

AC:

AN:

62682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33198

Middle Eastern (MID)

AF:

0.000409

AC:

AN:

2442

European-Non Finnish (NFE)

AF:

0.000199

AC:

AN:

316740

Other (OTH)

AF:

0.000132

AC:

AN:

30410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41426

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68040

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000212

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Roifman syndrome (3)

Osteodysplastic primordial dwarfism, type 1 (2)

Lowry-Wood syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

7.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000580972.2:n.50G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over