Variant 12-43730438-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.2044G>A(p.Asp682Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00099 in 1,613,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 1 hom. )

Consequence

PUS7L
NM_031292.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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 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=0.04213506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS7L	NM_031292.5 linkuse as main transcript	c.2044G>A	p.Asp682Asn	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.2044G>A	p.Asp682Asn	missense_variant	9/9	1	NM_031292.5	ENSP00000343081.5	Q9H0K6-1
PUS7L	ENST00000416848.6 linkuse as main transcript	c.2044G>A	p.Asp682Asn	missense_variant	9/9	1		ENSP00000415899.2	Q9H0K6-1
PUS7L	ENST00000551923.5 linkuse as main transcript	c.2044G>A	p.Asp682Asn	missense_variant	9/9	1		ENSP00000447706.1	Q9H0K6-1
PUS7L	ENST00000431332.7 linkuse as main transcript	c.1105G>A	p.Asp369Asn	missense_variant	8/8	2		ENSP00000398497.3	Q9H0K6-2

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000864

AC:

217

AN:

251206

Hom.:

AF XY:

0.000913

AC XY:

124

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000989

AC:

1445

AN:

1461470

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

703

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000999

AC:

152

AN:

152208

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000972

Hom.:

Bravo

AF:

0.000926

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000725

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000652

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 24, 2022

The c.2044G>A (p.D682N) 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 2044, causing the aspartic acid (D) at amino acid position 682 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0025

T;T;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

.;.;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.042

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;L;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.055

T;T;T;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.95

P;P;P;.

Vest4

0.26

MVP

0.39

MPC

0.056

ClinPred

0.026

GERP RS

4.1

Varity_R

0.18

gMVP

0.47

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