dbSNP rs529233430: USHBP1:p.Leu698Arg (chr19-17250244-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031941.4(USHBP1):c.2093T>G(p.Leu698Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,611,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

USHBP1
NM_031941.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

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:

ENSG00000269095 (HGNC:):

ENSG00000269095 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=0.08351964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USHBP1	NM_031941.4 link	c.2093T>G	p.Leu698Arg	missense_variant	Exon 13 of 13	ENST00000252597.8	NP_114147.2	Q8N6Y0-1A0A024R7H3
USHBP1	NM_001321417.2 link	c.2093T>G	p.Leu698Arg	missense_variant	Exon 13 of 13		NP_001308346.1	Q8N6Y0-1A0A024R7H3
USHBP1	NM_001297703.2 link	c.1901T>G	p.Leu634Arg	missense_variant	Exon 12 of 12		NP_001284632.1	Q8N6Y0G8JLM4B4DUE8
USHBP1	NR_135632.2 link	n.2334T>G		non_coding_transcript_exon_variant	Exon 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USHBP1	ENST00000252597.8 link	c.2093T>G	p.Leu698Arg	missense_variant	Exon 13 of 13	1	NM_031941.4	ENSP00000252597.2		Q8N6Y0-1
ENSG00000269095	ENST00000594059.1 link	c.-83+1338T>G		intron_variant	Intron 3 of 4	4		ENSP00000473056.1		M0R384

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

244470

Hom.:

AF XY:

0.0000376

AC XY:

AN XY:

132912

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000730

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1459426

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

725954

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000659

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.9

DANN

Benign

0.96

DEOGEN2

Benign

0.0042

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.042

Sift

Benign

0.032

D;D

Sift4G

Uncertain

0.049

D;T

Polyphen

0.72

P;.

Vest4

0.24

MutPred

0.13

Gain of methylation at L698 (P = 0.0202);.;

MVP

0.14

MPC

0.38

ClinPred

0.049

GERP RS

-1.1

Varity_R

0.25

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over