chr11-77130638-G-A

Variant names:

• chr11-77130638-G-A
• ENST00000409619:c.-110G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001369365.1(MYO7A):​c.-110G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000684 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO7A NM_001369365.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.4G>A	p.Val2Met	missense_variant	Exon 2 of 49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409619	c.-110G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 50	1		ENSP00000386635.2
MYO7A	ENST00000409709.9	c.4G>A	p.Val2Met	missense_variant	Exon 2 of 49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.4G>A	p.Val2Met	missense_variant	Exon 2 of 49	1		ENSP00000392185.2
MYO7A	ENST00000409619	c.-110G>A		5_prime_UTR_variant	Exon 2 of 50	1		ENSP00000386635.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461038 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726678

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Benign	1.4	L;.;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.0	N;.;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.012	D;.;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.81	P;.;.
Vest4		0.47
MutPred		0.45		Gain of disorder (P = 0.0721);Gain of disorder (P = 0.0721);Gain of disorder (P = 0.0721);
MVP		0.89
MPC		0.12
ClinPred		0.74	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-76841684;