NM_003802.3:c.5423C>A

Variant names:

• chr17-10306502-G-T
• rs182969555
• NM_003802.3:c.5423C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2 PP3_Moderate BS2

The NM_003802.3(MYH13):​c.5423C>A​(p.Ala1808Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000034 (0 hom.)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.96

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH13	NM_003802.3	c.5423C>A	p.Ala1808Glu	missense_variant	Exon 37 of 41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_001752791.3	n.96-10996G>T		intron_variant	Intron 1 of 4
LOC107985004	XR_007065617.1	n.96-10996G>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.5423C>A	p.Ala1808Glu	missense_variant	Exon 37 of 41	1	NM_003802.3	ENSP00000252172.4
MYH13	ENST00000621918.1	c.5423C>A	p.Ala1808Glu	missense_variant	Exon 35 of 39	1		ENSP00000480864.1
MYH13	ENST00000418404.8	c.5423C>A	p.Ala1808Glu	missense_variant	Exon 36 of 40	5		ENSP00000404570.3
ENSG00000273388	ENST00000609088.1	n.95-10996G>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251476 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

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.: 32

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;T;T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;.
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	4.3	H;H;H
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.7	.;.;D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.84
MutPred		0.65		Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);
MVP		0.90
MPC		0.47
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.89
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs182969555; hg19: chr17-10209819;