Variant 3-72750330-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018130.3(SHQ1):c.1688G>A(p.Arg563His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000941 in 1,613,712 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 2 hom. )

Consequence

SHQ1
NM_018130.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0320

Variant links:

Genes affected

SHQ1 (HGNC:25543): (SHQ1, H/ACA ribonucleoprotein assembly factor) SHQ1 assists in the assembly of H/ACA-box ribonucleoproteins that function in the processing of ribosomal RNAs, modification of spliceosomal small nuclear RNAs, and stabilization of telomerase (see MIM 602322) (Grozdanov et al., 2009 [PubMed 19383767]).[supplied by OMIM, Dec 2010]

SHQ1 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=0.009436309).

BP6

Variant 3-72750330-C-T is Benign according to our data. Variant chr3-72750330-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2352377.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHQ1	NM_018130.3 link	c.1688G>A	p.Arg563His	missense_variant	11/11	ENST00000325599.13	NP_060600.2	Q6PI26-1
SHQ1	XR_001740192.3 link	n.1287-22487G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHQ1	ENST00000325599.13 link	c.1688G>A	p.Arg563His	missense_variant	11/11	1	NM_018130.3	ENSP00000315182.8		Q6PI26-1

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000646

AC:

162

AN:

250900

Hom.:

AF XY:

0.000619

AC XY:

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000787

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000963

AC:

1408

AN:

1461558

Hom.:

Cov.:

AF XY:

0.000971

AC XY:

706

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000859

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000723

AC:

110

AN:

152154

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000932

Hom.:

Bravo

AF:

0.000729

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000717

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.85

DANN

Benign

0.12

DEOGEN2

Benign

0.00022

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0094

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

N;.

PrimateAI

Benign

0.19

PROVEAN

Benign

0.64

N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0

B;.

Vest4

0.042

MVP

0.040

MPC

0.070

ClinPred

0.0026

GERP RS

-2.1

Varity_R

0.013

gMVP

0.12

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