NM_000260.4:c.1004-35C>G

Variant names:

• chr11-77159412-C-G
• rs2071151
• NM_000260.4:c.1004-35C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000260.4(MYO7A):​c.1004-35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (992 hom., cov: 31)
  • Exomes 𝑓: 0.089 (8793 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0520
• Publications: 4 publications found

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia
• Usher syndrome type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant nonsyndromic hearing loss 11

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-77159412-C-G is Benign according to our data. Variant chr11-77159412-C-G is described in ClinVar as Benign. ClinVar VariationId is 255659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. 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
	MYO7A	NM_000260.4	MANE Select	c.1004-35C>G		intron	N/A	NP_000251.3
	MYO7A	NM_001127180.2		c.1004-35C>G		intron	N/A	NP_001120652.1
	MYO7A	NM_001369365.1		c.971-35C>G		intron	N/A	NP_001356294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.1004-35C>G		intron	N/A	ENSP00000386331.3
	MYO7A	ENST00000458637.6	TSL:1	c.1004-35C>G		intron	N/A	ENSP00000392185.2
	MYO7A	ENST00000409619.6	TSL:1	c.971-35C>G		intron	N/A	ENSP00000386635.2

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 14976 AN: 151056 Hom.: 988 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0534

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0992 AC: 23684 AN: 238868 AF XY: 0.0936

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.0861

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.0481

Gnomad NFE exome AF: 0.0546

Gnomad OTH exome AF: 0.0867

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0886 AC: 93178 AN: 1051362 Hom.: 8793 Cov.: 21 AF XY: 0.0866 AC XY: 46742 AN XY: 539900

African (AFR) AF: 0.201 AC: 5255 AN: 26206

American (AMR) AF: 0.140 AC: 6110 AN: 43668

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 2147 AN: 23258

East Asian (EAS) AF: 0.297 AC: 11228 AN: 37772

South Asian (SAS) AF: 0.102 AC: 7928 AN: 77854

European-Finnish (FIN) AF: 0.0468 AC: 2233 AN: 47690

Middle Eastern (MID) AF: 0.115 AC: 540 AN: 4704

European-Non Finnish (NFE) AF: 0.0714 AC: 53066 AN: 743164

Other (OTH) AF: 0.0993 AC: 4671 AN: 47046

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0992 AC: 14995 AN: 151172 Hom.: 992 Cov.: 31 AF XY: 0.0997 AC XY: 7361 AN XY: 73832

African (AFR) AF: 0.165 AC: 6768 AN: 41108

American (AMR) AF: 0.103 AC: 1562 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 300 AN: 3460

East Asian (EAS) AF: 0.282 AC: 1434 AN: 5080

South Asian (SAS) AF: 0.103 AC: 492 AN: 4758

European-Finnish (FIN) AF: 0.0467 AC: 489 AN: 10482

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.0535 AC: 3623 AN: 67776

Other (OTH) AF: 0.101 AC: 212 AN: 2094

Alfa AF: 0.0781 Hom.: 111

Bravo AF: 0.110

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 11 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 2 (1)
-	-	1	not specified (1)
-	-	1	Usher syndrome type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		-0.052
Mutation Taster		=26/74	disease causing

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: rs2071151; hg19: chr11-76870458; COSMIC: COSV68684107;