17-74920326-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_173477.5(USH1G):c.510C>G(p.Ala170Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000721 in 1,608,952 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

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

Exomes 𝑓: 0.000076 ( 2 hom. )

Consequence

USH1G
NM_173477.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.680

Variant links:

Genes affected

USH1G (HGNC:16356): (USH1 protein network component sans) This gene encodes a protein that contains three ankyrin domains, a class I PDZ-binding motif and a sterile alpha motif. The encoded protein interacts with harmonin, which is associated with Usher syndrome type 1C. This protein plays a role in the development and maintenance of the auditory and visual systems and functions in the cohesion of hair bundles formed by inner ear sensory cells. Mutations in this gene are associated with Usher syndrome type 1G (USH1G). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

USH1G links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 17-74920326-G-C is Benign according to our data. Variant chr17-74920326-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 48133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-74920326-G-C is described in Lovd as [Benign]. Variant chr17-74920326-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000755 (110/1456700) while in subpopulation MID AF= 0.00156 (9/5760). AF 95% confidence interval is 0.000815. There are 2 homozygotes in gnomad4_exome. There are 62 alleles in male gnomad4_exome subpopulation. Median coverage is 42. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1G	NM_173477.5 link	c.510C>G	p.Ala170Ala	synonymous_variant	Exon 2 of 3	ENST00000614341.5	NP_775748.2
USH1G	NM_001282489.3 link	c.201C>G	p.Ala67Ala	synonymous_variant	Exon 2 of 3		NP_001269418.1	Q495M9B4DL95
USH1G	XM_011524296.2 link	c.201C>G	p.Ala67Ala	synonymous_variant	Exon 2 of 3		XP_011522598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USH1G	ENST00000614341.5 link	c.510C>G	p.Ala170Ala	synonymous_variant	Exon 2 of 3	1	NM_173477.5	ENSP00000480279.1	Q495M9
USH1G	ENST00000579243.1 link	n.*109C>G		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000462568.1	J3KSN5
USH1G	ENST00000579243.1 link	n.*109C>G		3_prime_UTR_variant	Exon 2 of 3	2		ENSP00000462568.1	J3KSN5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000142

AC:

AN:

246188

Hom.:

AF XY:

0.000142

AC XY:

AN XY:

133884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000755

AC:

110

AN:

1456700

Hom.:

Cov.:

AF XY:

0.0000856

AC XY:

AN XY:

724546

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000452

Hom.:

Bravo

AF:

0.0000831

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 08, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

USH1G: BP4, BP7 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 25, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala170Ala in exon 2 of USH1G: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located near a splice junction. -

USH1G-related disorder

Benign:1

Jun 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.3

DANN

Benign

0.74

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