17-10303446-G-C

Position:

• chr17-10303446-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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]

ENSG00000273388 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH13	NM_003802.3	c.5519C>G	p.Ala1840Gly	missense_variant	38/41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_001752791.3	n.95+11533G>C		intron_variant
LOC107985004	XR_007065617.1	n.95+11533G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.5519C>G	p.Ala1840Gly	missense_variant	38/41	1	NM_003802.3	ENSP00000252172.4
MYH13	ENST00000621918.1	c.5519C>G	p.Ala1840Gly	missense_variant	36/39	1		ENSP00000480864.1
MYH13	ENST00000418404.8	c.5519C>G	p.Ala1840Gly	missense_variant	37/40	5		ENSP00000404570.3
ENSG00000273388	ENST00000609088.1	n.94+11533G>C		intron_variant		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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

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
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-10206763;