chr11-77147964-C-T

Variant names:

• chr11-77147964-C-T
• rs876657532
• NM_000260.4:c.285+14C>T

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_000260.4(MYO7A):c.285+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00000145 (AC=2) in the gnomAD database across 1,379,394 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00000031. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329
• Publications: 0 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):

• autosomal dominant nonsyndromic hearing loss 11

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

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive nonsyndromic hearing loss 2

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

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

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, 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

Classification according to ACGS-UK Somatic Oncogenicity v2025

Specifications for MYO7A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = 0.000000, AC = 2 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000260.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MYO7A NM_000260.4	MANE Select	c.285+14C>T	intron	Intron 4 of 48	Prot: NP_000251.3 UniProt:
	MYO7A NM_001127180.2		c.285+14C>T	intron	Intron 4 of 48	Prot: NP_001120652.1 UniProt:
	MYO7A NM_001369365.1		c.252+14C>T	intron	Intron 5 of 49	Prot: NP_001356294.1 UniProt:

MYO7A NM_000260.4

MANE Select

HGVSc / HGVSpc.285+14C>T

Exon rankIntron 4 of 48

intron

Prot: NP_000251.3UniProt: Q13402-1

MYO7A NM_001127180.2

HGVSc / HGVSpc.285+14C>T

Exon rankIntron 4 of 48

intron

Prot: NP_001120652.1UniProt: Q13402-2

MYO7A NM_001369365.1

HGVSc / HGVSpc.252+14C>T

Exon rankIntron 5 of 49

intron

Prot: NP_001356294.1UniProt: Q13402-8

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MYO7A ENST00000409709.9	TSL:1MANE Select	c.285+14C>T	intron	Intron 4 of 48	Prot: ENSP00000386331.3 UniProt:
	MYO7A ENST00000458637.6	TSL:1	c.285+14C>T	intron	Intron 4 of 48	Prot: ENSP00000392185.2 UniProt:
	MYO7A ENST00000409619.6	TSL:1	c.252+14C>T	intron	Intron 5 of 49	Prot: ENSP00000386635.2 UniProt:

MYO7A ENST00000409709.9

TSL:1MANE Select

HGVSc / HGVSpc.285+14C>T

Exon rankIntron 4 of 48

intron

Prot: ENSP00000386331.3UniProt: Q13402-1

MYO7A ENST00000458637.6

TSL:1

HGVSc / HGVSpc.285+14C>T

Exon rankIntron 4 of 48

intron

Prot: ENSP00000392185.2UniProt: Q13402-2

MYO7A ENST00000409619.6

TSL:1

HGVSc / HGVSpc.252+14C>T

Exon rankIntron 5 of 49

intron

Prot: ENSP00000386635.2UniProt: Q13402-8

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF: 0.00000145	AC:2	Hom:0	AN:1379394	Cov:34
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
TOPMed (Bravo)	AF: 0.00000378	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:0	AN:16840	Cov:

Showing 5 sources

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	5.5
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.94
GPN-Star LLR	N/A	-0.59
GPN-Star score	N/A	0.59
PhyloP100	Benign	0.33

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs876657532;

hg19: chr11-76859010;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar