rs1378890067

Variant names:

• chr15-43613234-G-T
• rs1378890067
• NM_153700.2:c.2481-3C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_153700.2(STRC):​c.2481-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000019 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 splice_region, intron
• Scores: Splicing: ADA: 0.9691
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

Genes affected

STRC (HGNC:16035): (stereocilin) This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]

STRC Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 16

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309475 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, max_spliceai. No scorers claiming Uncertain. Scorers claiming Benign: dbscSNV1_RF.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153700.2. 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
	STRC	NM_153700.2	MANE Select	c.2481-3C>A		splice_region intron	N/A	NP_714544.1	Q7RTU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	ENST00000450892.7	TSL:5 MANE Select	c.2481-3C>A		splice_region intron	N/A	ENSP00000401513.2	Q7RTU9
	STRC	ENST00000440125.5	TSL:1	n.*555C>A		non_coding_transcript_exon	Exon 9 of 28	ENSP00000394866.1	E7EPM8
	STRC	ENST00000440125.5	TSL:1	n.*555C>A		3_prime_UTR	Exon 9 of 28	ENSP00000394866.1	E7EPM8

Frequencies

GnomAD3 genomes AF: 0.0000191 AC: 1 AN: 52310 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000325

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 263840 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 143552

African (AFR) AF: 0.00 AC: 0 AN: 5324

American (AMR) AF: 0.00 AC: 0 AN: 14296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5618

East Asian (EAS) AF: 0.00 AC: 0 AN: 10842

South Asian (SAS) AF: 0.00 AC: 0 AN: 43804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 794

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 160804

Other (OTH) AF: 0.00 AC: 0 AN: 11996

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000191 AC: 1 AN: 52310 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 24548

African (AFR) AF: 0.00 AC: 0 AN: 5896

American (AMR) AF: 0.00 AC: 0 AN: 5288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1514

East Asian (EAS) AF: 0.00 AC: 0 AN: 2030

South Asian (SAS) AF: 0.00 AC: 0 AN: 1314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 170

European-Non Finnish (NFE) AF: 0.0000325 AC: 1 AN: 30748

Other (OTH) AF: 0.00 AC: 0 AN: 648

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.0
DANN	Benign	0.70
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Benign	0.46
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.59		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1378890067; hg19: chr15-43905432;