rs1555542172

Variant names:

• chr17-18130816-CAG-C
• rs1555542172
• NM_016239.4:c.4038+7_4038+8delAG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_016239.4(MYO15A):​c.4038+7_4038+8delAG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO15A NM_016239.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.458
• Publications: 0 publications found

Genes affected

MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]

MYO15A Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP6: Variant 17-18130816-CAG-C is Benign according to our data. Variant chr17-18130816-CAG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 164518.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO15A	NM_016239.4	MANE Select	c.4038+7_4038+8delAG		splice_region intron	N/A	NP_057323.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO15A	ENST00000647165.2	MANE Select	c.4038+7_4038+8delAG		splice_region intron	N/A	ENSP00000495481.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1267916 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 634350

African (AFR) AF: 0.00 AC: 0 AN: 27988

American (AMR) AF: 0.00 AC: 0 AN: 41096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23648

East Asian (EAS) AF: 0.00 AC: 0 AN: 35186

South Asian (SAS) AF: 0.00 AC: 0 AN: 77298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4880

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 958154

Other (OTH) AF: 0.00 AC: 0 AN: 52176

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 12, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

4038+7_4038+8del variant in intron 8 of MYO15A: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 0.15% (12/7996) European American chromosom es and in 0.23% (9/3964) African American chromosomes by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1555542172; hg19: chr17-18034130;