12-101290282-A-C

Variant summary

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

The NM_014503.3(UTP20):c.735+8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,583,346 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (66 hom.)
• Consequence: UTP20 NM_014503.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003658
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

Genes affected

UTP20 (HGNC:17897): (UTP20 small subunit processome component) UTP20 is a component of the U3 small nucleolar RNA (snoRNA) (SNORD3A; MIM 180710) protein complex (U3 snoRNP) and is involved in 18S rRNA processing (Wang et al., 2007 [PubMed 17498821]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-101290282-A-C is Benign according to our data. Variant chr12-101290282-A-C is described in ClinVar as [Benign]. Clinvar id is 773548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTP20	NM_014503.3	c.735+8A>C		splice_region_variant, intron_variant		ENST00000261637.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP20	ENST00000261637.5	c.735+8A>C		splice_region_variant, intron_variant		1	NM_014503.3	P1
UTP20	ENST00000551825.1	n.890+8A>C		splice_region_variant, intron_variant, non_coding_transcript_variant		1
UTP20	ENST00000551998.1	n.372+8A>C		splice_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00602 AC: 916 AN: 152216 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00687

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00867

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00673 AC: 1541 AN: 228834 Hom.: 11 AF XY: 0.00720 AC XY: 891 AN XY: 123828

Gnomad AFR exome AF: 0.000773

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00391

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.00589

Gnomad NFE exome AF: 0.00892

Gnomad OTH exome AF: 0.00604

GnomAD4 exome AF: 0.00682 AC: 9757 AN: 1431012 Hom.: 66 Cov.: 31 AF XY: 0.00713 AC XY: 5063 AN XY: 710346

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.00349

Gnomad4 ASJ exome AF: 0.00411

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.0119

Gnomad4 FIN exome AF: 0.00575

Gnomad4 NFE exome AF: 0.00707

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.00601 AC: 915 AN: 152334 Hom.: 8 Cov.: 32 AF XY: 0.00619 AC XY: 461 AN XY: 74502

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.00687

Gnomad4 NFE AF: 0.00867

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00662 Hom.: 1

Bravo AF: 0.00535

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.58
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.0
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

LitVar

Other links and lift over

dbSNP: rs111551110; hg19: chr12-101684060;