Variant chr6-145922812-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001042683.3(SHPRH):c.3570G>T(p.Gln1190His) variant causes a missense change. The variant allele was found at a frequency of 0.0000596 in 1,610,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

SHPRH
NM_001042683.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

SHPRH (HGNC:19336): (SNF2 histone linker PHD RING helicase) SHPRH is a ubiquitously expressed protein that contains motifs characteristics of several DNA repair proteins, transcription factors, and helicases. SHPRH is a functional homolog of S. cerevisiae RAD5 (Unk et al., 2006 [PubMed 17108083]).[supplied by OMIM, Mar 2008]

SHPRH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, SHPRH

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHPRH	NM_001042683.3 linkuse as main transcript	c.3570G>T	p.Gln1190His	missense_variant	19/30	ENST00000275233.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHPRH	ENST00000275233.12 linkuse as main transcript	c.3570G>T	p.Gln1190His	missense_variant	19/30	1	NM_001042683.3	P1	Q149N8-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000526

AC:

AN:

246936

Hom.:

AF XY:

0.0000597

AC XY:

AN XY:

134038

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:

0.0000657

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.0000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000617

AC:

AN:

1458996

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

725824

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:

0.0000349

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000766

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151942

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000646

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000366

AC:

ExAC

AF:

0.0000662

AC:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.000179

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 27, 2023

The c.3570G>T (p.Q1190H) alteration is located in exon 19 (coding exon 18) of the SHPRH gene. This alteration results from a G to T substitution at nucleotide position 3570, causing the glutamine (Q) at amino acid position 1190 to be replaced by a histidine (H). 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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.0053

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;.;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.1

M;.;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.7

N;N;.;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.018

D;D;.;D

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.76

MutPred

0.39

Gain of sheet (P = 4e-04);.;.;Gain of sheet (P = 4e-04);

MVP

0.77

MPC

0.72

ClinPred

0.22

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.58

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