Variant 19-17250244-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_031941.4(USHBP1):c.2093T>C(p.Leu698Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,611,738 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

USHBP1
NM_031941.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0100308955).

BP6

Variant 19-17250244-A-G is Benign according to our data. Variant chr19-17250244-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2211715.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USHBP1	NM_031941.4 linkuse as main transcript	c.2093T>C	p.Leu698Pro	missense_variant	13/13	ENST00000252597.8
USHBP1	NM_001321417.2 linkuse as main transcript	c.2093T>C	p.Leu698Pro	missense_variant	13/13
USHBP1	NM_001297703.2 linkuse as main transcript	c.1901T>C	p.Leu634Pro	missense_variant	12/12
USHBP1	NR_135632.2 linkuse as main transcript	n.2334T>C		non_coding_transcript_exon_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USHBP1	ENST00000252597.8 linkuse as main transcript	c.2093T>C	p.Leu698Pro	missense_variant	13/13	1	NM_031941.4	P1	Q8N6Y0-1
USHBP1	ENST00000431146.6 linkuse as main transcript	c.1901T>C	p.Leu634Pro	missense_variant	12/12	2
USHBP1	ENST00000324554.9 linkuse as main transcript	c.*1059T>C		3_prime_UTR_variant, NMD_transcript_variant	14/14	2
USHBP1	ENST00000597928.5 linkuse as main transcript	c.*3213T>C		3_prime_UTR_variant, NMD_transcript_variant	12/12	2			Q8N6Y0-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000695

AC:

AN:

244470

Hom.:

AF XY:

0.0000527

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:

0.000668

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1459426

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000859

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

May 01, 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

0.052

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.9

DANN

Benign

0.63

DEOGEN2

Benign

0.0031

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.0070

Sift

Benign

0.13

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.0010

B;.

Vest4

0.093

MutPred

0.14

Gain of glycosylation at L698 (P = 0.0242);.;

MVP

0.061

MPC

0.24

ClinPred

0.013

GERP RS

-1.1

Varity_R

0.11

gMVP

0.10

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