Variant 17-74916911-GCA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_173477.5(USH1G):c.*1160_*1161delTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000906 in 152,362 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0062 ( 0 hom. )

Consequence

USH1G
NM_173477.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.691

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000872 (132/151390) while in subpopulation AFR AF= 0.00204 (84/41240). AF 95% confidence interval is 0.00169. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
USH1G	NM_173477.5 link	c.1160_1161delTG	3_prime_UTR_variant	3/3	ENST00000614341.5	NP_775748.2
USH1G	NM_001282489.3 link	c.1160_1161delTG	3_prime_UTR_variant	3/3		NP_001269418.1	Q495M9B4DL95
USH1G	XM_011524296.2 link	c.1160_1161delTG	3_prime_UTR_variant	3/3		XP_011522598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1G	ENST00000614341 link	c.1160_1161delTG		3_prime_UTR_variant	3/3	1	NM_173477.5	ENSP00000480279.1		Q495M9

Frequencies

GnomAD3 genomes

AF:

0.000866

AC:

131

AN:

151272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000369

Gnomad OTH

AF:

0.00145

GnomAD4 exome

AF:

0.00617

AC:

AN:

972

Hom.:

AF XY:

0.00421

AC XY:

AN XY:

712

show subpopulations

Gnomad4 AFR exome

AF:

0.0556

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:

0.00575

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.000872

AC:

132

AN:

151390

Hom.:

Cov.:

AF XY:

0.000865

AC XY:

AN XY:

73974

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00105

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.000369

Gnomad4 OTH

AF:

0.00143

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis pigmentosa-deafness syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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