5-16670860-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012334.3(MYO10):c.5549C>T(p.Pro1850Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYO10 NM_012334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38064104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO10	NM_012334.3	c.5549C>T	p.Pro1850Leu	missense_variant	39/41	ENST00000513610.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO10	ENST00000513610.6	c.5549C>T	p.Pro1850Leu	missense_variant	39/41	1	NM_012334.3	P1
RETREG1-AS1	ENST00000653650.1	n.330-7974G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461708 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727136

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2022

The c.5549C>T (p.P1850L) alteration is located in exon 39 (coding exon 39) of the MYO10 gene. This alteration results from a C to T substitution at nucleotide position 5549, causing the proline (P) at amino acid position 1850 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	21
Dann	Benign	0.68
DEOGEN2	Benign	0.030	T;T;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;D;.;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.30	T
REVEL	Benign	0.28
Sift4G	Benign	0.23	T;T;D;D
Polyphen		0.014	.;B;.;.
Vest4		0.56
MutPred		0.55		.;Loss of catalytic residue at P1849 (P = 0.0195);.;.;
MVP		0.63
MPC		0.20
ClinPred		0.16	T
GERP RS		5.0
Varity_R		0.14
gMVP		0.32

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: chr5-16670969;