Variant 7-105470772-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_019042.5(PUS7):c.1314A>G(p.Leu438=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,612,766 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0077 ( 17 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 18 hom. )

Consequence

PUS7
NM_019042.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.784

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 7-105470772-T-C is Benign according to our data. Variant chr7-105470772-T-C is described in ClinVar as [Benign]. Clinvar id is 3033867.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.784 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00773 (1177/152296) while in subpopulation AFR AF= 0.0269 (1119/41560). AF 95% confidence interval is 0.0256. There are 17 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7	NM_019042.5 linkuse as main transcript	c.1314A>G	p.Leu438=	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.1314A>G	p.Leu438=	synonymous_variant	11/16	1	NM_019042.5	P1	Q96PZ0-1
PUS7	ENST00000356362.6 linkuse as main transcript	c.1314A>G	p.Leu438=	synonymous_variant	11/16	2		P1	Q96PZ0-1
PUS7	ENST00000478208.1 linkuse as main transcript	n.134A>G		non_coding_transcript_exon_variant	2/2	3
PUS7	ENST00000481939.5 linkuse as main transcript	c.1314A>G	p.Leu438=	synonymous_variant, NMD_transcript_variant	11/17	5

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1179

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00201

AC:

504

AN:

251296

Hom.:

AF XY:

0.00152

AC XY:

206

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0274

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000813

AC:

1188

AN:

1460470

Hom.:

Cov.:

AF XY:

0.000717

AC XY:

521

AN XY:

726374

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.00773

AC:

1177

AN:

152296

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

529

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0269

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.00878

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PUS7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 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

-0.51

CADD

Benign

1.7

DANN

Benign

0.77

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