rs7927472

Variant names:

• chr11-77199721-C-T
• rs7927472
• NM_000260.4:c.4755C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-77199721-C-T
• chr11-77199721-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000260.4(MYO7A):​c.4755C>T​(p.Ser1585Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,612,982 control chromosomes in the GnomAD database, including 222,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17986 hom., cov: 32)
  • Exomes 𝑓: 0.52 (204172 hom.)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 2.84
• Publications: 22 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 Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Usher syndrome type 1

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

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

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-77199721-C-T is Benign according to our data. Variant chr11-77199721-C-T is described in ClinVar as Benign. ClinVar VariationId is 43257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

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.4755C>T	p.Ser1585Ser	synonymous	Exon 35 of 49	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.4641C>T	p.Ser1547Ser	synonymous	Exon 35 of 49	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.4608C>T	p.Ser1536Ser	synonymous	Exon 36 of 50	NP_001356294.1	Q13402-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.4755C>T	p.Ser1585Ser	synonymous	Exon 35 of 49	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.4641C>T	p.Ser1547Ser	synonymous	Exon 35 of 49	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.4608C>T	p.Ser1536Ser	synonymous	Exon 36 of 50	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72128 AN: 151978 Hom.: 17976 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.492

GnomAD2 exomes AF: 0.514 AC: 127220 AN: 247600 AF XY: 0.505

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.641

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.485

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.524 AC: 765649 AN: 1460886 Hom.: 204172 Cov.: 51 AF XY: 0.519 AC XY: 377181 AN XY: 726700

African (AFR) AF: 0.313 AC: 10469 AN: 33474

American (AMR) AF: 0.633 AC: 28239 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 10340 AN: 26120

East Asian (EAS) AF: 0.475 AC: 18855 AN: 39678

South Asian (SAS) AF: 0.363 AC: 31312 AN: 86180

European-Finnish (FIN) AF: 0.620 AC: 32960 AN: 53200

Middle Eastern (MID) AF: 0.402 AC: 2321 AN: 5768

European-Non Finnish (NFE) AF: 0.541 AC: 601504 AN: 1111504

Other (OTH) AF: 0.491 AC: 29649 AN: 60346

GnomAD4 genome AF: 0.474 AC: 72159 AN: 152096 Hom.: 17986 Cov.: 32 AF XY: 0.479 AC XY: 35589 AN XY: 74348

African (AFR) AF: 0.323 AC: 13414 AN: 41492

American (AMR) AF: 0.575 AC: 8800 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2423 AN: 5168

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4816

European-Finnish (FIN) AF: 0.620 AC: 6564 AN: 10582

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36331 AN: 67954

Other (OTH) AF: 0.491 AC: 1037 AN: 2112

Alfa AF: 0.498 Hom.: 14308

Bravo AF: 0.470

Asia WGS AF: 0.402 AC: 1398 AN: 3478

EpiCase AF: 0.527

EpiControl AF: 0.527

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 11 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 2 (2)
-	-	2	Usher syndrome type 1 (2)
-	-	1	Usher syndrome type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		2.8
Mutation Taster		=93/7	polymorphism (auto)

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: rs7927472; hg19: chr11-76910766; COSMIC: COSV68687506; COSMIC: COSV68687506;