chr6-75915362-T-A

Variant names:

• chr6-75915362-T-A
• rs699186
• NM_004999.4:c.*350T>A

Variant summary

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

The NM_001368865.1(MYO6):​c.*350T>A variant causes a 3 prime UTR 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO6 NM_001368865.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 8 publications found

Genes affected

MYO6 (HGNC:7605): (myosin VI) This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

MYO6 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 22

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

  Inheritance: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, G2P
• autosomal recessive nonsyndromic hearing loss 37

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368865.1. 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
	MYO6	NM_004999.4	MANE Select	c.*350T>A		3_prime_UTR	Exon 35 of 35	NP_004990.3
	MYO6	NM_001368865.1		c.*350T>A		3_prime_UTR	Exon 36 of 36	NP_001355794.1
	MYO6	NM_001368866.1		c.*350T>A		3_prime_UTR	Exon 35 of 35	NP_001355795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO6	ENST00000369977.8	TSL:1 MANE Select	c.*350T>A		3_prime_UTR	Exon 35 of 35	ENSP00000358994.3
	MYO6	ENST00000664640.1		c.*350T>A		3_prime_UTR	Exon 36 of 36	ENSP00000499278.1
	MYO6	ENST00000947981.1		c.*350T>A		3_prime_UTR	Exon 36 of 36	ENSP00000618040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 186420 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 100508

African (AFR) AF: 0.00 AC: 0 AN: 5562

American (AMR) AF: 0.00 AC: 0 AN: 7926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4720

East Asian (EAS) AF: 0.00 AC: 0 AN: 8174

South Asian (SAS) AF: 0.00 AC: 0 AN: 33784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 107350

Other (OTH) AF: 0.00 AC: 0 AN: 9478

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 14081

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.43

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: rs699186; hg19: chr6-76625079;