NM_153676.4:c.1801C>G

Variant names:

• chr11-17509568-G-C
• NM_153676.4:c.1801C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153676.4(USH1C):​c.1801C>G​(p.Pro601Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,734 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.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: USH1C NM_153676.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

Genes affected

USH1C (HGNC:12597): (USH1 protein network component harmonin) This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38453403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4	c.1801C>G	p.Pro601Ala	missense_variant	Exon 18 of 27	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.1285-7588C>G		intron_variant	Intron 15 of 20	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.1801C>G	p.Pro601Ala	missense_variant	Exon 18 of 27	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.1285-7588C>G		intron_variant	Intron 15 of 20	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445734 Hom.: 0 Cov.: 39 AF XY: 0.00000139 AC XY: 1 AN XY: 716864

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.073
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.042	D
Vest4		0.52
MutPred		0.12		Loss of glycosylation at P601 (P = 0.006);
MVP		0.55
MPC		0.061
ClinPred		0.98	D
GERP RS		5.2
gMVP		0.35

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: chr11-17531115;