Variant chr12-43748597-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031292.5(PUS7L):c.923G>T(p.Arg308Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,583,336 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

PUS7L
NM_031292.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.118

Variant links:

Genes affected

PUS7L (HGNC:25276): (pseudouridine synthase 7 like) Predicted to enable pseudouridine synthase activity. Predicted to be involved in pseudouridine synthesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PUS7L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1680131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7L	NM_031292.5 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	3/9	ENST00000344862.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS7L	ENST00000344862.10 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	3/9	1	NM_031292.5	P1	Q9H0K6-1

Frequencies

GnomAD3 genomes

AF:

0.000389

AC:

AN:

151732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00250

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000255

AC:

AN:

219928

Hom.:

AF XY:

0.000268

AC XY:

AN XY:

119434

show subpopulations

Gnomad AFR exome

AF:

0.0000643

Gnomad AMR exome

AF:

0.000915

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000123

Gnomad FIN exome

AF:

0.0000488

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000175

AC:

250

AN:

1431492

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

132

AN XY:

711800

show subpopulations

Gnomad4 AFR exome

AF:

0.0000321

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.000122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.000289

GnomAD4 genome

AF:

0.000395

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00256

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000205

Hom.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000264

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.923G>T (p.R308L) alteration is located in exon 3 (coding exon 2) of the PUS7L gene. This alteration results from a G to T substitution at nucleotide position 923, causing the arginine (R) at amino acid position 308 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

T;T;T

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.019

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

MutationTaster

Benign

0.53

D;D;D;D

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.85

P;P;P

Vest4

0.69

MVP

0.59

MPC

0.13

ClinPred

0.042

GERP RS

1.9

Varity_R

0.20

gMVP

0.53

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