Variant 7-105470697-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_019042.5(PUS7):c.1389A>G(p.Ala463=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,594,362 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 30 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 24 hom. )

Consequence

PUS7
NM_019042.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.115

Variant links:

Genes affected

PUS7 (HGNC:26033): (pseudouridine synthase 7) Enables enzyme binding activity and pseudouridine synthase activity. Involved in several processes, including pseudouridine synthesis; regulation of hematopoietic stem cell differentiation; and regulation of mesoderm development. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PUS7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 7-105470697-T-C is Benign according to our data. Variant chr7-105470697-T-C is described in ClinVar as [Benign]. Clinvar id is 785229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.115 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1790/152356) while in subpopulation AFR AF= 0.0408 (1696/41578). AF 95% confidence interval is 0.0392. There are 30 homozygotes in gnomad4. There are 871 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7	NM_019042.5 linkuse as main transcript	c.1389A>G	p.Ala463=	synonymous_variant	11/16	ENST00000469408.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS7	ENST00000469408.6 linkuse as main transcript	c.1389A>G	p.Ala463=	synonymous_variant	11/16	1	NM_019042.5	P1	Q96PZ0-1
PUS7	ENST00000356362.6 linkuse as main transcript	c.1389A>G	p.Ala463=	synonymous_variant	11/16	2		P1	Q96PZ0-1
PUS7	ENST00000478208.1 linkuse as main transcript	n.209A>G		non_coding_transcript_exon_variant	2/2	3
PUS7	ENST00000481939.5 linkuse as main transcript	c.1325+64A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1777

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00310

AC:

767

AN:

247446

Hom.:

AF XY:

0.00230

AC XY:

308

AN XY:

133820

show subpopulations

Gnomad AFR exome

AF:

0.0390

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00192

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000204

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00128

AC:

1847

AN:

1442006

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

804

AN XY:

714248

show subpopulations

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00252

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.0117

AC:

1790

AN:

152356

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

871

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2018	- -

PUS7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.8

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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