Variant 19-17251595-A-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_031941.4(USHBP1):c.1909T>C(p.Cys637Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,613,824 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000040 ( 1 hom. )

Consequence

USHBP1
NM_031941.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

USHBP1 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=0.15644154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USHBP1	NM_031941.4 linkuse as main transcript	c.1909T>C	p.Cys637Arg	missense_variant	12/13	ENST00000252597.8
USHBP1	NM_001321417.2 linkuse as main transcript	c.1909T>C	p.Cys637Arg	missense_variant	12/13
USHBP1	NM_001297703.2 linkuse as main transcript	c.1717T>C	p.Cys573Arg	missense_variant	11/12
USHBP1	NR_135632.2 linkuse as main transcript	n.2150T>C		non_coding_transcript_exon_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USHBP1	ENST00000252597.8 linkuse as main transcript	c.1909T>C	p.Cys637Arg	missense_variant	12/13	1	NM_031941.4	P1	Q8N6Y0-1
USHBP1	ENST00000431146.6 linkuse as main transcript	c.1717T>C	p.Cys573Arg	missense_variant	11/12	2
USHBP1	ENST00000324554.9 linkuse as main transcript	c.*875T>C		3_prime_UTR_variant, NMD_transcript_variant	13/14	2
USHBP1	ENST00000597928.5 linkuse as main transcript	c.*3029T>C		3_prime_UTR_variant, NMD_transcript_variant	11/12	2			Q8N6Y0-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251430

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

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

Oct 18, 2021

The c.1909T>C (p.C637R) alteration is located in exon 12 (coding exon 11) of the USHBP1 gene. This alteration results from a T to C substitution at nucleotide position 1909, causing the cysteine (C) at amino acid position 637 to be replaced by an arginine (R). 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

Uncertain

0.44

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Benign

0.68

DEOGEN2

Benign

0.022

T;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.20

Sift

Benign

0.29

T;T

Sift4G

Benign

0.077

T;T

Polyphen

0.97

D;.

Vest4

0.68

MVP

0.25

MPC

0.67

ClinPred

0.16

GERP RS

4.4

Varity_R

0.38

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