17-74923081-G-C

Variant names:

• chr17-74923081-G-C
• rs769903865
• NM_173477.5:c.-8C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173477.5(USH1G):​c.-8C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: USH1G NM_173477.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

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]

OTOP2 (HGNC:19657): (otopetrin 2) Predicted to enable proton channel activity. Predicted to be involved in proton transmembrane transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173477.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH1G	NM_173477.5	MANE Select	c.-8C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_775748.2
	USH1G	NM_173477.5	MANE Select	c.-8C>G		5_prime_UTR	Exon 1 of 3	NP_775748.2
	USH1G	NM_001282489.3		c.-264C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001269418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH1G	ENST00000614341.5	TSL:1 MANE Select	c.-8C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000480279.1
	USH1G	ENST00000614341.5	TSL:1 MANE Select	c.-8C>G		5_prime_UTR	Exon 1 of 3	ENSP00000480279.1
	OTOP2	ENST00000580223.2	TSL:1	c.-231+47G>C		intron	N/A	ENSP00000463837.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		3.0
PromoterAI		-0.074	Neutral

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

Other links and lift over

dbSNP: rs769903865; hg19: chr17-72919176;