chr17-10306998-C-G

Variant names:

• chr17-10306998-C-G
• NM_003802.3:c.5236G>C

Variant summary

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

The NM_003802.3(MYH13):​c.5236G>C​(p.Glu1746Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,706 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: 7.87

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.5236G>C	p.Glu1746Gln	missense_variant	Exon 36 of 41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_001752791.3	n.96-10500C>G		intron_variant	Intron 1 of 4
LOC107985004	XR_007065617.1	n.96-10500C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.5236G>C	p.Glu1746Gln	missense_variant	Exon 36 of 41	1	NM_003802.3	ENSP00000252172.4
MYH13	ENST00000621918.1	c.5236G>C	p.Glu1746Gln	missense_variant	Exon 34 of 39	1		ENSP00000480864.1
MYH13	ENST00000418404.8	c.5236G>C	p.Glu1746Gln	missense_variant	Exon 35 of 40	5		ENSP00000404570.3
ENSG00000273388	ENST00000609088.1	n.95-10500C>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461706 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;T
Eigen	Pathogenic	0.80
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;D;.
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Pathogenic	3.2	M;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.1	.;.;N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0090	.;.;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.28
MutPred		0.58		Loss of phosphorylation at S1748 (P = 0.1373);Loss of phosphorylation at S1748 (P = 0.1373);Loss of phosphorylation at S1748 (P = 0.1373);
MVP		0.87
MPC		0.18
ClinPred		0.94	D
GERP RS		3.1
Varity_R		0.36
gMVP		0.82

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: chr17-10210315; COSMIC: COSV52833864;