rs3744550

Positions:

• chr17-10303278-T-C

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1862Q) 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYH13	NM_003802.3	c.5585A>G	p.His1862Arg	missense_variant	39/41	ENST00000252172.9
LOC107985004	XR_007065617.1	n.95+11365T>C		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3	n.95+11365T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH13	ENST00000252172.9	c.5585A>G	p.His1862Arg	missense_variant	39/41	1	NM_003802.3	P1
MYH13	ENST00000621918.1	c.5585A>G	p.His1862Arg	missense_variant	37/39	1		P1
	ENST00000609088.1	n.94+11365T>C		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8	c.5585A>G	p.His1862Arg	missense_variant	38/40	5		P1

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

GnomAD3 exomes AF: 0.125 AC: 31175 AN: 249804 Hom.: 2769 AF XY: 0.125 AC XY: 17004 AN XY: 135492

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 SAS exome AF: 0.212

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

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.0788

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.0715

Gnomad4 NFE exome AF: 0.0705

Gnomad4 OTH exome AF: 0.103

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0877

Alfa AF: 0.0816 Hom.: 1124

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
MutationTaster	Benign	1.0	P;P;P
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

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