rs3744550

Variant names:

• chr17-10303278-T-C
• rs3744550
• NM_003802.3:c.5585A>G

Variant summary

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

The NM_003802.3(MYH13):​c.5585A>G​(p.His1862Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,613,780 control chromosomes in the GnomAD database, including 9,690 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1862Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.11 (1164 hom., cov: 32)
  • Exomes 𝑓: 0.091 (8526 hom.)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• 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=0.0014390349).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH13	NM_003802.3	c.5585A>G	p.His1862Arg	missense_variant	Exon 39 of 41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_001752791.3	n.95+11365T>C		intron_variant	Intron 1 of 4
LOC107985004	XR_007065617.1	n.95+11365T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.5585A>G	p.His1862Arg	missense_variant	Exon 39 of 41	1	NM_003802.3	ENSP00000252172.4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16546 AN: 151958 Hom.: 1155 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0819

GnomAD2 exomes AF: 0.125 AC: 31175 AN: 249804 AF XY: 0.125

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.0788

Gnomad EAS exome AF: 0.337

Gnomad FIN exome AF: 0.0728

Gnomad NFE exome AF: 0.0722

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0912 AC: 133290 AN: 1461704 Hom.: 8526 Cov.: 32 AF XY: 0.0943 AC XY: 68583 AN XY: 727158

African (AFR) AF: 0.146 AC: 4887 AN: 33476

American (AMR) AF: 0.149 AC: 6678 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 2059 AN: 26116

East Asian (EAS) AF: 0.319 AC: 12678 AN: 39694

South Asian (SAS) AF: 0.207 AC: 17834 AN: 86232

European-Finnish (FIN) AF: 0.0715 AC: 3817 AN: 53416

Middle Eastern (MID) AF: 0.118 AC: 678 AN: 5766

European-Non Finnish (NFE) AF: 0.0705 AC: 78423 AN: 1111896

Other (OTH) AF: 0.103 AC: 6236 AN: 60388

GnomAD4 genome AF: 0.109 AC: 16595 AN: 152076 Hom.: 1164 Cov.: 32 AF XY: 0.112 AC XY: 8331 AN XY: 74334

African (AFR) AF: 0.144 AC: 5968 AN: 41490

American (AMR) AF: 0.128 AC: 1954 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.332 AC: 1702 AN: 5132

South Asian (SAS) AF: 0.210 AC: 1008 AN: 4808

European-Finnish (FIN) AF: 0.0712 AC: 754 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0692 AC: 4704 AN: 67990

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.0847 Hom.: 1783

Bravo AF: 0.113

TwinsUK AF: 0.0677 AC: 251

ALSPAC AF: 0.0763 AC: 294

ESP6500AA AF: 0.141 AC: 601

ESP6500EA AF: 0.0685 AC: 584

ExAC AF: 0.127 AC: 15349

Asia WGS AF: 0.273 AC: 949 AN: 3478

EpiCase AF: 0.0719

EpiControl AF: 0.0732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.1
DANN	Benign	0.33
DEOGEN2	Benign	0.092	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.47	.;T;.
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	N;N;N
PhyloP100		-1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	2.6	.;.;N
REVEL	Benign	0.19
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.038
MPC		0.12
ClinPred		0.0037	T
GERP RS		0.54
Varity_R		0.046
gMVP		0.078
Mutation Taster		=100/0	polymorphism (auto)

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: rs3744550; hg19: chr17-10206595; COSMIC: COSV52829009;