Variant 12-43736528-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031292.5(PUS7L):c.1578G>A(p.Met526Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000197 in 1,614,086 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 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

PUS7L
NM_031292.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27795315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS7L	NM_031292.5 linkuse as main transcript	c.1578G>A	p.Met526Ile	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.1578G>A	p.Met526Ile	missense_variant	7/9	1	NM_031292.5	ENSP00000343081.5	Q9H0K6-1
PUS7L	ENST00000416848.6 linkuse as main transcript	c.1578G>A	p.Met526Ile	missense_variant	7/9	1		ENSP00000415899.2	Q9H0K6-1
PUS7L	ENST00000551923.5 linkuse as main transcript	c.1578G>A	p.Met526Ile	missense_variant	7/9	1		ENSP00000447706.1	Q9H0K6-1
PUS7L	ENST00000431332.7 linkuse as main transcript	c.639G>A	p.Met213Ile	missense_variant	6/8	2		ENSP00000398497.3	Q9H0K6-2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000203

AC:

AN:

251474

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000205

AC:

300

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

153

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000118

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000278

Hom.:

Bravo

AF:

0.000113

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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 21, 2021

The c.1578G>A (p.M526I) 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 1578, causing the methionine (M) at amino acid position 526 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

T;T;T;.

Eigen

Benign

-0.0031

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

.;.;T;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.087

T;T;T;T

Sift4G

Benign

0.76

T;T;T;T

Polyphen

0.059

B;B;B;.

Vest4

0.53

MutPred

0.66

Gain of catalytic residue at H524 (P = 0.005);Gain of catalytic residue at H524 (P = 0.005);Gain of catalytic residue at H524 (P = 0.005);.;

MVP

0.33

MPC

0.043

ClinPred

0.068

GERP RS

5.0

Varity_R

0.24

gMVP

0.59

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