Variant 7-105481072-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1

The NM_019042.5(PUS7):c.1155C>A(p.Val385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,611,458 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 1 hom. )

Consequence

PUS7
NM_019042.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.241

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 -12 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP6

Variant 7-105481072-G-T is Benign according to our data. Variant chr7-105481072-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 715610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000742 (113/152284) while in subpopulation AFR AF= 0.00257 (107/41564). AF 95% confidence interval is 0.00218. There are 0 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7	NM_019042.5 linkuse as main transcript	c.1155C>A	p.Val385=	synonymous_variant	9/16	ENST00000469408.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS7	ENST00000469408.6 linkuse as main transcript	c.1155C>A	p.Val385=	synonymous_variant	9/16	1	NM_019042.5	P1	Q96PZ0-1
PUS7	ENST00000356362.6 linkuse as main transcript	c.1155C>A	p.Val385=	synonymous_variant	9/16	2		P1	Q96PZ0-1
PUS7	ENST00000481939.5 linkuse as main transcript	c.1155C>A	p.Val385=	synonymous_variant, NMD_transcript_variant	9/17	5

Frequencies

GnomAD3 genomes

AF:

0.000716

AC:

109

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000177

AC:

AN:

249198

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

134722

show subpopulations

Gnomad AFR exome

AF:

0.00248

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000555

AC:

AN:

1459174

Hom.:

Cov.:

AF XY:

0.0000482

AC XY:

AN XY:

725850

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152284

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000660

Hom.:

Bravo

AF:

0.000695

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	PUS7: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2018	- -

PUS7-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 19, 2019

This variant is classified as likely 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

5.0

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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