rs201525855

Variant names:

• chr17-74920158-G-A
• NM_173477.5:c.678C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-74920158-G-A
• chr17-74920158-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_173477.5(USH1G):​c.678C>T​(p.Gly226Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,449,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G226G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: USH1G NM_173477.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.512 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1G	NM_173477.5	c.678C>T	p.Gly226Gly	synonymous_variant	Exon 2 of 3	ENST00000614341.5	NP_775748.2
USH1G	NM_001282489.3	c.369C>T	p.Gly123Gly	synonymous_variant	Exon 2 of 3		NP_001269418.1
USH1G	XM_011524296.2	c.369C>T	p.Gly123Gly	synonymous_variant	Exon 2 of 3		XP_011522598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1G	ENST00000614341.5	c.678C>T	p.Gly226Gly	synonymous_variant	Exon 2 of 3	1	NM_173477.5	ENSP00000480279.1
USH1G	ENST00000579243.1	n.*277C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000462568.1
USH1G	ENST00000579243.1	n.*277C>T		3_prime_UTR_variant	Exon 2 of 3	2		ENSP00000462568.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1449606 Hom.: 0 Cov.: 42 AF XY: 0.00000554 AC XY: 4 AN XY: 721756

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.7
DANN	Benign	0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-72916253;