17-10303446-G-C

Variant names:

• chr17-10303446-G-C
• NM_003802.3:c.5519C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003802.3(MYH13):​c.5519C>G​(p.Ala1840Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH13	NM_003802.3	c.5519C>G	p.Ala1840Gly	missense_variant	Exon 38 of 41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_001752791.3	n.95+11533G>C		intron_variant	Intron 1 of 4
LOC107985004	XR_007065617.1	n.95+11533G>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.5519C>G	p.Ala1840Gly	missense_variant	Exon 38 of 41	1	NM_003802.3	ENSP00000252172.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5519C>G (p.A1840G) alteration is located in exon 38 (coding exon 36) of the MYH13 gene. This alteration results from a C to G substitution at nucleotide position 5519, causing the alanine (A) at amino acid position 1840 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	.;D;.
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.7	M;M;M
PhyloP100		5.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	.;.;N
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	.;.;D
Sift4G	Benign	0.062	T;T;T
Polyphen		0.32	B;B;B
Vest4		0.60
MutPred		0.66		Loss of stability (P = 0.0738);Loss of stability (P = 0.0738);Loss of stability (P = 0.0738);
MVP		0.76
MPC		0.23
ClinPred		0.91	D
GERP RS		3.9
Varity_R		0.32
gMVP		0.13

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

hg19: chr17-10206763;