Variant 3-72750834-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018130.3(SHQ1):c.1184C>T(p.Ser395Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000111 in 1,353,726 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SHQ1
NM_018130.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHQ1	NM_018130.3 link	c.1184C>T	p.Ser395Phe	missense_variant, splice_region_variant	11/11	ENST00000325599.13	NP_060600.2	Q6PI26-1
SHQ1	XR_001740192.3 link	n.1287-22991C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHQ1	ENST00000325599.13 link	c.1184C>T	p.Ser395Phe	missense_variant, splice_region_variant	11/11	1	NM_018130.3	ENSP00000315182.8		Q6PI26-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000492

AC:

AN:

122020

Hom.:

AF XY:

0.0000612

AC XY:

AN XY:

65382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1353726

Hom.:

Cov.:

AF XY:

0.0000121

AC XY:

AN XY:

663490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000178

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000809

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

May 08, 2024

The c.1184C>T (p.S395F) alteration is located in exon 11 (coding exon 11) of the SHQ1 gene. This alteration results from a C to T substitution at nucleotide position 1184, causing the serine (S) at amino acid position 395 to be replaced by a phenylalanine (F). 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

0.29

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

T;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;.

Vest4

0.62

MutPred

0.72

Loss of disorder (P = 0.0313);.;

MVP

0.61

MPC

0.39

ClinPred

0.77

GERP RS

5.0

Varity_R

0.40

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