NM_003802.3:c.3211A>G

Variant names:

• chr17-10320397-T-C
• rs2074877
• NM_003802.3:c.3211A>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.3211A>G​(p.Met1071Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,611,744 control chromosomes in the GnomAD database, including 302,694 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 0.61 (28747 hom., cov: 33)
  • Exomes 𝑓: 0.61 (273947 hom.)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 36 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=2.289554E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	NM_003802.3	MANE Select	c.3211A>G	p.Met1071Val	missense	Exon 25 of 41	NP_003793.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	ENST00000252172.9	TSL:1 MANE Select	c.3211A>G	p.Met1071Val	missense	Exon 25 of 41	ENSP00000252172.4
	MYH13	ENST00000621918.1	TSL:1	c.3211A>G	p.Met1071Val	missense	Exon 23 of 39	ENSP00000480864.1
	MYH13	ENST00000418404.8	TSL:5	c.3211A>G	p.Met1071Val	missense	Exon 24 of 40	ENSP00000404570.3

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93177 AN: 152046 Hom.: 28712 Cov.: 33

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.617

GnomAD2 exomes AF: 0.595 AC: 146361 AN: 246104 AF XY: 0.587

Gnomad AFR exome AF: 0.637

Gnomad AMR exome AF: 0.666

Gnomad ASJ exome AF: 0.641

Gnomad EAS exome AF: 0.438

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.609

GnomAD4 exome AF: 0.610 AC: 890567 AN: 1459580 Hom.: 273947 Cov.: 46 AF XY: 0.605 AC XY: 439244 AN XY: 725954

African (AFR) AF: 0.630 AC: 21089 AN: 33454

American (AMR) AF: 0.662 AC: 29412 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 16769 AN: 26086

East Asian (EAS) AF: 0.435 AC: 17258 AN: 39666

South Asian (SAS) AF: 0.468 AC: 40224 AN: 85906

European-Finnish (FIN) AF: 0.589 AC: 31364 AN: 53278

Middle Eastern (MID) AF: 0.607 AC: 3499 AN: 5766

European-Non Finnish (NFE) AF: 0.625 AC: 694649 AN: 1110654

Other (OTH) AF: 0.602 AC: 36303 AN: 60308

GnomAD4 genome AF: 0.613 AC: 93264 AN: 152164 Hom.: 28747 Cov.: 33 AF XY: 0.605 AC XY: 44994 AN XY: 74402

African (AFR) AF: 0.637 AC: 26426 AN: 41500

American (AMR) AF: 0.618 AC: 9457 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2199 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2261 AN: 5168

South Asian (SAS) AF: 0.463 AC: 2233 AN: 4822

European-Finnish (FIN) AF: 0.575 AC: 6093 AN: 10592

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42526 AN: 67994

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.621 Hom.: 132264

Bravo AF: 0.621

TwinsUK AF: 0.636 AC: 2359

ALSPAC AF: 0.620 AC: 2390

ESP6500AA AF: 0.648 AC: 2418

ESP6500EA AF: 0.630 AC: 5157

ExAC AF: 0.591 AC: 71361

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.000023	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.23
Sift	Uncertain	0.017	D
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.087
MPC		0.097
ClinPred		0.0099	T
GERP RS		1.3
Varity_R		0.22
gMVP		0.28
Mutation Taster		=99/1	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: rs2074877; hg19: chr17-10223714; COSMIC: COSV52821186; COSMIC: COSV52821186;