Variant 12-43730381-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031292.5(PUS7L):c.2101G>A(p.Val701Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000726 in 1,612,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

PUS7L
NM_031292.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.210

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004580587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS7L	NM_031292.5 linkuse as main transcript	c.2101G>A	p.Val701Ile	missense_variant	9/9	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.2101G>A	p.Val701Ile	missense_variant	9/9	1	NM_031292.5	ENSP00000343081.5	Q9H0K6-1
PUS7L	ENST00000416848.6 linkuse as main transcript	c.2101G>A	p.Val701Ile	missense_variant	9/9	1		ENSP00000415899.2	Q9H0K6-1
PUS7L	ENST00000551923.5 linkuse as main transcript	c.2101G>A	p.Val701Ile	missense_variant	9/9	1		ENSP00000447706.1	Q9H0K6-1
PUS7L	ENST00000431332.7 linkuse as main transcript	c.1162G>A	p.Val388Ile	missense_variant	8/8	2		ENSP00000398497.3	Q9H0K6-2

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000132

AC:

AN:

250378

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000459

AC:

AN:

1459900

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726288

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000328

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00108

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:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000723

Hom.:

Bravo

AF:

0.000419

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Oct 16, 2024

The c.2101G>A (p.V701I) alteration is located in exon 9 (coding exon 8) of the PUS7L gene. This alteration results from a G to A substitution at nucleotide position 2101, causing the valine (V) at amino acid position 701 to be replaced by an isoleucine (I). 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

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.3

DANN

Benign

0.84

DEOGEN2

Benign

0.00047

T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.59

.;.;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.39

N;N;N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.23

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.89

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0020

B;B;B;.

Vest4

0.026

MVP

0.15

MPC

0.029

ClinPred

0.0027

GERP RS

-1.4

Varity_R

0.035

gMVP

0.062

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