Variant chr17-76274109-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001388453.1(QRICH2):c.5634G>T(p.Thr1878Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,584,116 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 3 hom. )

Consequence

QRICH2
NM_001388453.1 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.156

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007110387).

BP6

Variant 17-76274109-C-A is Benign according to our data. Variant chr17-76274109-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1176695.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=-0.156 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRICH2	NM_001388453.1 linkuse as main transcript	c.5634G>T	p.Thr1878Thr	synonymous_variant	19/19	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.5634G>T	p.Thr1878Thr	synonymous_variant	19/19		NM_001388453.1	ENSP00000504874.1		A0A7P0T7G7

Frequencies

GnomAD3 genomes

AF:

0.000913

AC:

139

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000899

AC:

191

AN:

212360

Hom.:

AF XY:

0.000778

AC XY:

AN XY:

118204

show subpopulations

Gnomad AFR exome

AF:

0.000156

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000754

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.000679

AC:

972

AN:

1431752

Hom.:

Cov.:

AF XY:

0.000681

AC XY:

485

AN XY:

712678

show subpopulations

Gnomad4 AFR exome

AF:

0.000354

Gnomad4 AMR exome

AF:

0.00138

Gnomad4 ASJ exome

AF:

0.00827

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.000532

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.000912

AC:

139

AN:

152364

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.00111

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000722

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	QRICH2: BP4, BP7 -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.53

DANN

Benign

0.80

DEOGEN2

Benign

0.027

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0071

MetaSVM

Benign

-0.86

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.14

Sift

Pathogenic

0.0

MVP

0.17

ClinPred

0.061

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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