17-10303494-C-A

Variant names:

• chr17-10303494-C-A
• NM_003802.3:c.5471G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003802.3(MYH13):​c.5471G>T​(p.Arg1824Leu) 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 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659

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 rank	MANE	Protein	UniProt
MYH13	NM_003802.3	c.5471G>T	p.Arg1824Leu	missense_variant	Exon 38 of 41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_001752791.3	n.95+11581C>A		intron_variant	Intron 1 of 4
LOC107985004	XR_007065617.1	n.95+11581C>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.5471G>T	p.Arg1824Leu	missense_variant	Exon 38 of 41	1	NM_003802.3	ENSP00000252172.4
MYH13	ENST00000621918.1	c.5471G>T	p.Arg1824Leu	missense_variant	Exon 36 of 39	1		ENSP00000480864.1
MYH13	ENST00000418404.8	c.5471G>T	p.Arg1824Leu	missense_variant	Exon 37 of 40	5		ENSP00000404570.3
ENSG00000273388	ENST00000609088.1	n.94+11581C>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461432 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727032

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;T;T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.080
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.95	.;D;.
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Uncertain	0.071	D
MutationAssessor	Pathogenic	3.9	H;H;H
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.5	.;.;D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.95	P;P;P
Vest4		0.52
MutPred		0.63		Loss of MoRF binding (P = 0.0246);Loss of MoRF binding (P = 0.0246);Loss of MoRF binding (P = 0.0246);
MVP		0.78
MPC		0.14
ClinPred		0.98	D
GERP RS		1.9
Varity_R		0.54
gMVP		0.34

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: chr17-10206811; COSMIC: COSV99352334;