Variant 17-76277266-C-G 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.5162G>C(p.Arg1721Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: -0.659

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=0.13670385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRICH2	NM_001388453.1 linkuse as main transcript	c.5162G>C	p.Arg1721Pro	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.5162G>C	p.Arg1721Pro	missense_variant	16/19		NM_001388453.1	ENSP00000504874.1		A0A7P0T7G7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236216

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000597

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:

6.90e-7

AC:

AN:

1448930

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

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.:

Bravo

AF:

0.00000756

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

Mar 26, 2024

The c.4664G>C (p.R1555P) alteration is located in exon 16 (coding exon 16) of the QRICH2 gene. This alteration results from a G to C substitution at nucleotide position 4664, causing the arginine (R) at amino acid position 1555 to be replaced by a proline (P). 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

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.9

DANN

Benign

0.91

DEOGEN2

Benign

0.0056

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

.;L

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.1

.;D

REVEL

Benign

0.040

Sift

Benign

0.24

.;T

Sift4G

Benign

0.33

.;T

Polyphen

0.011

.;B

Vest4

0.25

MutPred

0.35

.;Gain of glycosylation at S1559 (P = 0.0858);

MVP

0.030

MPC

0.28

ClinPred

0.11

GERP RS

1.4

Varity_R

0.32

gMVP

0.43

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