NM_003802.3:c.3881G>A

Variant names:

• chr17-10315796-C-T
• rs17690195
• NM_003802.3:c.3881G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003802.3(MYH13):​c.3881G>A​(p.Arg1294Gln) variant causes a missense change. The variant allele was found at a frequency of 0.16 in 1,613,796 control chromosomes in the GnomAD database, including 21,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1566 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19940 hom.)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.19
• Publications: 23 publications found

Genes affected

MYH13 (HGNC:7571): (myosin heavy chain 13) Predicted to enable microfilament motor activity. Predicted to be involved in muscle contraction. Predicted to act upstream of or within cellular response to starvation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985004 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016312599).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003802.3. 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
	MYH13	NM_003802.3	MANE Select	c.3881G>A	p.Arg1294Gln	missense	Exon 29 of 41	NP_003793.2	Q9UKX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	ENST00000252172.9	TSL:1 MANE Select	c.3881G>A	p.Arg1294Gln	missense	Exon 29 of 41	ENSP00000252172.4	Q9UKX3
	MYH13	ENST00000621918.1	TSL:1	c.3881G>A	p.Arg1294Gln	missense	Exon 27 of 39	ENSP00000480864.1	Q9UKX3
	MYH13	ENST00000418404.8	TSL:5	c.3881G>A	p.Arg1294Gln	missense	Exon 28 of 40	ENSP00000404570.3	Q9UKX3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20500 AN: 152050 Hom.: 1567 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.168 AC: 41765 AN: 249214 AF XY: 0.171

Gnomad AFR exome AF: 0.0680

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.162 AC: 237135 AN: 1461628 Hom.: 19940 Cov.: 33 AF XY: 0.164 AC XY: 119595 AN XY: 727096

African (AFR) AF: 0.0684 AC: 2289 AN: 33478

American (AMR) AF: 0.171 AC: 7638 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4364 AN: 26136

East Asian (EAS) AF: 0.175 AC: 6959 AN: 39700

South Asian (SAS) AF: 0.240 AC: 20708 AN: 86258

European-Finnish (FIN) AF: 0.187 AC: 10003 AN: 53402

Middle Eastern (MID) AF: 0.157 AC: 907 AN: 5768

European-Non Finnish (NFE) AF: 0.158 AC: 175222 AN: 1111796

Other (OTH) AF: 0.150 AC: 9045 AN: 60368

GnomAD4 genome AF: 0.135 AC: 20491 AN: 152168 Hom.: 1566 Cov.: 32 AF XY: 0.139 AC XY: 10374 AN XY: 74382

African (AFR) AF: 0.0691 AC: 2870 AN: 41536

American (AMR) AF: 0.124 AC: 1898 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3470

East Asian (EAS) AF: 0.162 AC: 837 AN: 5160

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4816

European-Finnish (FIN) AF: 0.203 AC: 2145 AN: 10592

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10624 AN: 67986

Other (OTH) AF: 0.131 AC: 278 AN: 2116

Alfa AF: 0.144 Hom.: 5016

Bravo AF: 0.125

TwinsUK AF: 0.172 AC: 637

ALSPAC AF: 0.156 AC: 600

ESP6500AA AF: 0.0593 AC: 236

ESP6500EA AF: 0.153 AC: 1276

ExAC AF: 0.164 AC: 19861

Asia WGS AF: 0.182 AC: 636 AN: 3478

EpiCase AF: 0.144

EpiControl AF: 0.148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.4	N
PhyloP100		6.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.048
MPC		0.11
ClinPred		0.027	T
GERP RS		3.0
Varity_R		0.046
gMVP		0.11
Mutation Taster		=90/10	polymorphism (auto)

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: rs17690195; hg19: chr17-10219113; COSMIC: COSV52822179; COSMIC: COSV52822179;