rs1341567

Variant names:

• chr6-75918459-A-C
• rs1341567
• NM_004999.4:c.*3447A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-75918459-A-C
• chr6-75918459-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004999.4(MYO6):​c.*3447A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,200 control chromosomes in the GnomAD database, including 7,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene MYO6 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.18 (7878 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MYO6 NM_004999.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.391
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• nonsyndromic genetic hearing loss

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

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: 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

Specifications for MYO6 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-75918459-A-C is Benign according to our data. Variant chr6-75918459-A-C is described in ClinVar as Benign. ClinVar VariationId is 358042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004999.4. 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
	MYO6	NM_004999.4	MANE Select	c.*3447A>C		3_prime_UTR	Exon 35 of 35	NP_004990.3
	MYO6	NM_001368865.1		c.*3447A>C		3_prime_UTR	Exon 36 of 36	NP_001355794.1	A0A590UJ40
	MYO6	NM_001368866.1		c.*3447A>C		3_prime_UTR	Exon 35 of 35	NP_001355795.1	A0A1Y0BRN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO6	ENST00000369977.8	TSL:1 MANE Select	c.*3447A>C		3_prime_UTR	Exon 35 of 35	ENSP00000358994.3	Q9UM54-1
	MYO6	ENST00000664640.1		c.*3447A>C		3_prime_UTR	Exon 36 of 36	ENSP00000499278.1	A0A590UJ40
	MYO6	ENST00000927893.1		c.*3447A>C		3_prime_UTR	Exon 33 of 33	ENSP00000597952.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27157 AN: 152082 Hom.: 7864 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.00541

Gnomad OTH AF: 0.133

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.179 AC: 27220 AN: 152200 Hom.: 7878 Cov.: 32 AF XY: 0.173 AC XY: 12838 AN XY: 74416

African (AFR) AF: 0.608 AC: 25191 AN: 41464

American (AMR) AF: 0.0794 AC: 1214 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.00541 AC: 368 AN: 68014

Other (OTH) AF: 0.132 AC: 279 AN: 2114

Alfa AF: 0.0481 Hom.: 3400

Bravo AF: 0.204

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant nonsyndromic hearing loss 22 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 37 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.67
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1341567; hg19: chr6-76628176;