Variant 17-10303212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003802.3(MYH13):c.5651G>A(p.Arg1884Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYH13
NM_003802.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.837

Variant links:

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]

MYH13 links:

ENSG00000273388 (HGNC:):

ENSG00000273388 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16661954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH13	NM_003802.3 linkuse as main transcript	c.5651G>A	p.Arg1884Lys	missense_variant	39/41	ENST00000252172.9	NP_003793.2	Q9UKX3
LOC107985004	XR_001752791.3 linkuse as main transcript	n.95+11299C>T		intron_variant
LOC107985004	XR_007065617.1 linkuse as main transcript	n.95+11299C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYH13	ENST00000252172.9 linkuse as main transcript	c.5651G>A	p.Arg1884Lys	missense_variant	39/41	1	NM_003802.3	ENSP00000252172.4	Q9UKX3
MYH13	ENST00000621918.1 linkuse as main transcript	c.5651G>A	p.Arg1884Lys	missense_variant	37/39	1		ENSP00000480864.1	Q9UKX3
MYH13	ENST00000418404.8 linkuse as main transcript	c.5651G>A	p.Arg1884Lys	missense_variant	38/40	5		ENSP00000404570.3	Q9UKX3
ENSG00000273388	ENST00000609088.1 linkuse as main transcript	n.94+11299C>T		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.5651G>A (p.R1884K) alteration is located in exon 39 (coding exon 37) of the MYH13 gene. This alteration results from a G to A substitution at nucleotide position 5651, causing the arginine (R) at amino acid position 1884 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.82

.;T;.

M_CAP

Benign

0.021

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

M;M;M

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

.;.;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.013

.;.;D

Sift4G

Benign

0.19

T;T;T

Polyphen

0.0050

B;B;B

Vest4

0.12

MutPred

0.67

Gain of ubiquitination at R1884 (P = 0.0177);Gain of ubiquitination at R1884 (P = 0.0177);Gain of ubiquitination at R1884 (P = 0.0177);

MVP

0.59

MPC

0.099

ClinPred

0.20

GERP RS

1.7

Varity_R

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over