Variant chr12-43736566-C-T 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.1540G>A(p.Gly514Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000725 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

PUS7L
NM_031292.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.76

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=0.24757048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS7L	NM_031292.5 linkuse as main transcript	c.1540G>A	p.Gly514Ser	missense_variant	7/9	ENST00000344862.10	NP_112582.3	Q9H0K6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PUS7L	ENST00000344862.10 linkuse as main transcript	c.1540G>A	p.Gly514Ser	missense_variant	7/9	1	NM_031292.5	ENSP00000343081.5	Q9H0K6-1
PUS7L	ENST00000416848.6 linkuse as main transcript	c.1540G>A	p.Gly514Ser	missense_variant	7/9	1		ENSP00000415899.2	Q9H0K6-1
PUS7L	ENST00000551923.5 linkuse as main transcript	c.1540G>A	p.Gly514Ser	missense_variant	7/9	1		ENSP00000447706.1	Q9H0K6-1
PUS7L	ENST00000431332.7 linkuse as main transcript	c.601G>A	p.Gly201Ser	missense_variant	6/8	2		ENSP00000398497.3	Q9H0K6-2

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000478

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

251458

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.0000578

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:

0.0000424

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000361

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.0000653

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:

0.000473

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

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

Feb 14, 2023

The c.1540G>A (p.G514S) alteration is located in exon 7 (coding exon 6) of the PUS7L gene. This alteration results from a G to A substitution at nucleotide position 1540, causing the glycine (G) at amino acid position 514 to be replaced by a serine (S). 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

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;T;T;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;.;D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.0

M;M;M;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Benign

0.072

T;T;T;T

Polyphen

1.0

D;D;D;.

Vest4

0.74

MVP

0.59

MPC

0.23

ClinPred

0.31

GERP RS

5.0

Varity_R

0.61

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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