Variant 17-76275933-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388453.1(QRICH2):c.5368A>G(p.Lys1790Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,826 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

QRICH2
NM_001388453.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0730

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10230523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRICH2	NM_001388453.1 linkuse as main transcript	c.5368A>G	p.Lys1790Glu	missense_variant	18/19	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.5368A>G	p.Lys1790Glu	missense_variant	18/19		NM_001388453.1	ENSP00000504874.1		A0A7P0T7G7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244562

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

132982

show subpopulations

Gnomad AFR exome

AF:

0.0000618

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455826

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724492

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 21, 2024

The c.4870A>G (p.K1624E) alteration is located in exon 18 (coding exon 18) of the QRICH2 gene. This alteration results from a A to G substitution at nucleotide position 4870, causing the lysine (K) at amino acid position 1624 to be replaced by a glutamic acid (E). 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

0.25

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.1

.;N

REVEL

Benign

0.015

Sift

Uncertain

0.0060

.;D

Sift4G

Uncertain

0.022

.;D

Polyphen

0.76

.;P

Vest4

0.21

MutPred

0.28

.;Loss of methylation at K1624 (P = 0.0017);

MVP

0.040

MPC

0.28

ClinPred

0.16

GERP RS

2.8

Varity_R

0.18

gMVP

0.24

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