17-10306496-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003802.3(MYH13):c.5429A>G(p.Lys1810Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 6.23

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2924437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH13	NM_003802.3	c.5429A>G	p.Lys1810Arg	missense_variant	37/41	ENST00000252172.9
LOC107985004	XR_007065617.1	n.96-11002T>C		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3	n.96-11002T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH13	ENST00000252172.9	c.5429A>G	p.Lys1810Arg	missense_variant	37/41	1	NM_003802.3	P1
MYH13	ENST00000621918.1	c.5429A>G	p.Lys1810Arg	missense_variant	35/39	1		P1
	ENST00000609088.1	n.95-11002T>C		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8	c.5429A>G	p.Lys1810Arg	missense_variant	36/40	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

May 03, 2023

The c.5429A>G (p.K1810R) alteration is located in exon 37 (coding exon 35) of the MYH13 gene. This alteration results from a A to G substitution at nucleotide position 5429, causing the lysine (K) at amino acid position 1810 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Benign	-0.0059	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	0.70	N;N;N
PrimateAI	Uncertain	0.73	T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.45	B;B;B
Vest4		0.39
MutPred		0.43		Loss of ubiquitination at K1810 (P = 0.0148);Loss of ubiquitination at K1810 (P = 0.0148);Loss of ubiquitination at K1810 (P = 0.0148);
MVP		0.73
MPC		0.079
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.24
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-10209813;