NM_012334.3:c.6071G>C

Variant names:

• chr5-16668281-C-G
• rs77404051
• NM_012334.3:c.6071G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/21 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03
• Publications: 6 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: Benign. The variant received -20 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 VariationId is 788980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

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.6071G>C	p.Ser2024Thr	missense	Exon 40 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.6071G>C	p.Ser2024Thr	missense	Exon 40 of 41	ENSP00000421280.1	Q9HD67-1
	MYO10	ENST00000274203.13	TSL:5	c.6104G>C	p.Ser2035Thr	missense	Exon 40 of 41	ENSP00000274203.10	A0A0A0MQX1
	MYO10	ENST00000505695.5	TSL:2	c.4088G>C	p.Ser1363Thr	missense	Exon 22 of 23	ENSP00000421170.1	E9PEW5

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

GnomAD2 exomes AF: 0.00391 AC: 950 AN: 243214 AF XY: 0.00284

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 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

African (AFR) AF: 0.0525 AC: 1742 AN: 33212

American (AMR) AF: 0.00321 AC: 139 AN: 43304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000823 AC: 7 AN: 85104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00437 AC: 25 AN: 5726

European-Non Finnish (NFE) AF: 0.000103 AC: 114 AN: 1110024

Other (OTH) AF: 0.00368 AC: 221 AN: 60124

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

African (AFR) AF: 0.0489 AC: 2032 AN: 41552

American (AMR) AF: 0.00471 AC: 72 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68038

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.66	N
PhyloP100		1.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.21
Sift	Benign	0.41	T
Sift4G	Benign	0.73	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
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs77404051; hg19: chr5-16668390;