5-16668281-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012334.3(MYO10):c.6071G>C(p.Ser2024Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,608,546 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (34 hom.)
• Consequence: MYO10 NM_012334.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033227801).
• BP6: Variant 5-16668281-C-G is Benign according to our data. Variant chr5-16668281-C-G is described in ClinVar as [Benign]. Clinvar id is 788980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO10	NM_012334.3	c.6071G>C	p.Ser2024Thr	missense_variant	40/41	ENST00000513610.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO10	ENST00000513610.6	c.6071G>C	p.Ser2024Thr	missense_variant	40/41	1	NM_012334.3	P1
RETREG1-AS1	ENST00000653650.1	n.330-10553C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2126 AN: 152190 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00391 AC: 950 AN: 243214 Hom.: 9 AF XY: 0.00284 AC XY: 375 AN XY: 131958

Gnomad AFR exome AF: 0.0528

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000683

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000180

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.00154 AC: 2248 AN: 1456238 Hom.: 34 Cov.: 31 AF XY: 0.00133 AC XY: 965 AN XY: 724290

Gnomad4 AFR exome AF: 0.0525

Gnomad4 AMR exome AF: 0.00321

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000823

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.0140 AC: 2128 AN: 152308 Hom.: 46 Cov.: 32 AF XY: 0.0133 AC XY: 994 AN XY: 74474

Gnomad4 AFR AF: 0.0489

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00239 Hom.: 3

Bravo AF: 0.0163

ESP6500AA AF: 0.0479 AC: 187

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00453 AC: 547

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	17
Dann	Benign	0.94
DEOGEN2	Benign	0.026	T;T;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.77	T;T;.;T
MetaRNN	Benign	0.0033	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
REVEL	Benign	0.21
Sift4G	Benign	0.73	T;T;T;T
Polyphen		0.031	.;B;.;.
Vest4		0.36
MVP		0.61
MPC		0.16
ClinPred		0.0098	T
GERP RS		4.3
Varity_R		0.13
gMVP		0.26

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: rs77404051; hg19: chr5-16668390;