11-77184616-C-T

Position:

• chr11-77184616-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000260.4(MYO7A):​c.3404C>T​(p.Ser1135Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a domain MyTH4 1 (size 236) in uniprot entity MYO7A_HUMAN there are 26 pathogenic changes around while only 4 benign (87%) in NM_000260.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25518817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.3404C>T	p.Ser1135Phe	missense_variant	27/49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.3404C>T	p.Ser1135Phe	missense_variant	27/49	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.3404C>T	p.Ser1135Phe	missense_variant	27/49	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3371C>T	p.Ser1124Phe	missense_variant	28/50	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.947C>T	p.Ser316Phe	missense_variant	7/29	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1244C>T		non_coding_transcript_exon_variant	10/32			ENSP00000499323.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.33	T;T;.;.;.;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.3	L;.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.2	N;.;N;N;.;N
REVEL	Uncertain	0.31
Sift	Benign	0.14	T;.;T;T;.;T
Sift4G	Uncertain	0.040	D;T;D;D;.;T
Polyphen		0.0	B;.;.;.;.;.
Vest4		0.64
MutPred		0.32		Loss of disorder (P = 0.0138);.;Loss of disorder (P = 0.0138);.;.;.;
MVP		0.94
MPC		0.10
ClinPred		0.64	D
GERP RS		5.0
Varity_R		0.16
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-76895661;