5-16670845-T-C

Variant names:

• chr5-16670845-T-C
• rs201810628
• NM_012334.3:c.5564A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012334.3(MYO10):​c.5564A>G​(p.Tyr1855Cys) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1855F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO10 NM_012334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 1 publications found

Genes affected

MYO10 (HGNC:7593): (myosin X) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-10 (MYH10). Unconventional myosins contain the basic domains of conventional myosins and are further distinguished from class members by their tail domains. This gene functions as an actin-based molecular motor and plays a role in integration of F-actin and microtubule cytoskeletons during meiosis. [provided by RefSeq, Dec 2011]

RETREG1-AS1 (HGNC:55551): (RETREG1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012334.3. 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
	MYO10	NM_012334.3	MANE Select	c.5564A>G	p.Tyr1855Cys	missense	Exon 39 of 41	NP_036466.2	Q9HD67-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO10	ENST00000513610.6	TSL:1 MANE Select	c.5564A>G	p.Tyr1855Cys	missense	Exon 39 of 41	ENSP00000421280.1	Q9HD67-1
	MYO10	ENST00000274203.13	TSL:5	c.5597A>G	p.Tyr1866Cys	missense	Exon 39 of 41	ENSP00000274203.10	A0A0A0MQX1
	MYO10	ENST00000505695.5	TSL:2	c.3581A>G	p.Tyr1194Cys	missense	Exon 21 of 23	ENSP00000421170.1	E9PEW5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.48		Loss of phosphorylation at Y1855 (P = 0.0591)
MVP		0.60
MPC		0.82
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.60
gMVP		0.59
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201810628; hg19: chr5-16670954;