Variant 17-76277218-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001388453.1(QRICH2):c.5210C>T(p.Pro1737Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,602,712 control chromosomes in the GnomAD database, including 4,923 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 2405 hom., cov: 33)

Exomes 𝑓: 0.029 ( 2518 hom. )

Consequence

QRICH2
NM_001388453.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.432

Variant links:

Genes affected

QRICH2 (HGNC:25326): (glutamine rich 2) Involved in cell projection assembly; flagellated sperm motility; and negative regulation of ubiquitin-dependent protein catabolic process. Located in sperm flagellum. Implicated in spermatogenic failure 35. [provided by Alliance of Genome Resources, Apr 2022]

QRICH2 links:

QRICH2 (HGNC:):

QRICH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017457008).

BP6

Variant 17-76277218-G-A is Benign according to our data. Variant chr17-76277218-G-A is described in ClinVar as [Benign]. Clinvar id is 3055373.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRICH2	NM_001388453.1 linkuse as main transcript	c.5210C>T	p.Pro1737Leu	missense_variant	16/19	ENST00000680821.2	NP_001375382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QRICH2	ENST00000680821.2 linkuse as main transcript	c.5210C>T	p.Pro1737Leu	missense_variant	16/19		NM_001388453.1	ENSP00000504874.1		A0A7P0T7G7

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16893

AN:

152034

Hom.:

2395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.0386

Gnomad SAS

AF:

0.0403

Gnomad FIN

AF:

0.0294

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0823

GnomAD3 exomes

AF:

0.0476

AC:

11381

AN:

239044

Hom.:

1111

AF XY:

0.0416

AC XY:

5414

AN XY:

130286

show subpopulations

Gnomad AFR exome

AF:

0.354

Gnomad AMR exome

AF:

0.0308

Gnomad ASJ exome

AF:

0.0523

Gnomad EAS exome

AF:

0.0413

Gnomad SAS exome

AF:

0.0358

Gnomad FIN exome

AF:

0.0296

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0371

GnomAD4 exome

AF:

0.0287

AC:

41687

AN:

1450560

Hom.:

2518

Cov.:

AF XY:

0.0279

AC XY:

20180

AN XY:

722092

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.0341

Gnomad4 ASJ exome

AF:

0.0524

Gnomad4 EAS exome

AF:

0.0488

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0271

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0462

GnomAD4 genome

AF:

0.111

AC:

16948

AN:

152152

Hom.:

2405

Cov.:

AF XY:

0.109

AC XY:

8145

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.334

Gnomad4 AMR

AF:

0.0507

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.0387

Gnomad4 SAS

AF:

0.0406

Gnomad4 FIN

AF:

0.0294

Gnomad4 NFE

AF:

0.0177

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0367

Hom.:

651

Bravo

AF:

0.124

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0202

AC:

ESP6500AA

AF:

0.341

AC:

1502

ESP6500EA

AF:

0.0173

AC:

149

ExAC

AF:

0.0523

AC:

6355

Asia WGS

AF:

0.0780

AC:

270

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

QRICH2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.6

DANN

Benign

0.77

DEOGEN2

Benign

0.0017

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.62

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.1

.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.36

.;N

REVEL

Benign

0.028

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0040

.;B

Vest4

0.072

MPC

0.17

ClinPred

0.00087

GERP RS

-2.5

Varity_R

0.036

gMVP

0.15

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