5-16668420-C-T

Variant names:

• chr5-16668420-C-T
• rs763181078
• NM_012334.3:c.5932G>A

Variant summary

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

The NM_012334.3(MYO10):​c.5932G>A​(p.Asp1978Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,322 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000013 (1 hom.)
• Consequence: MYO10 NM_012334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74

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=0.28002557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO10	NM_012334.3	c.5932G>A	p.Asp1978Asn	missense_variant	Exon 40 of 41	ENST00000513610.6	NP_036466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO10	ENST00000513610.6	c.5932G>A	p.Asp1978Asn	missense_variant	Exon 40 of 41	1	NM_012334.3	ENSP00000421280.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000241 AC: 6 AN: 248506 Hom.: 0 AF XY: 0.0000223 AC XY: 3 AN XY: 134792

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461322 Hom.: 1 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 726950

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: 0.000220

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5932G>A (p.D1978N) alteration is located in exon 40 (coding exon 40) of the MYO10 gene. This alteration results from a G to A substitution at nucleotide position 5932, causing the aspartic acid (D) at amino acid position 1978 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D;D;.;D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Uncertain	-0.058	T
MutationAssessor	Benign	0.34	.;N;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.2	.;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.11	.;T;T;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.11	.;B;.;.
Vest4		0.38
MutPred		0.27		.;Loss of stability (P = 0.1514);.;.;
MVP		0.78
MPC		0.24
ClinPred		0.13	T
GERP RS		5.1
Varity_R		0.095
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs763181078; hg19: chr5-16668529;