chr17-10306988-A-C

Variant names:

• chr17-10306988-A-C
• rs761931528
• NM_003802.3:c.5246T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003802.3(MYH13):​c.5246T>G​(p.Ile1749Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1749T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47
• Publications: 0 publications found

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]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985004 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30685544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003802.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	NM_003802.3	MANE Select	c.5246T>G	p.Ile1749Ser	missense	Exon 36 of 41	NP_003793.2	Q9UKX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	ENST00000252172.9	TSL:1 MANE Select	c.5246T>G	p.Ile1749Ser	missense	Exon 36 of 41	ENSP00000252172.4	Q9UKX3
	MYH13	ENST00000621918.1	TSL:1	c.5246T>G	p.Ile1749Ser	missense	Exon 34 of 39	ENSP00000480864.1	Q9UKX3
	MYH13	ENST00000418404.8	TSL:5	c.5246T>G	p.Ile1749Ser	missense	Exon 35 of 40	ENSP00000404570.3	Q9UKX3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.5
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Benign	0.089	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.42
MutPred		0.62		Loss of stability (P = 0.0332)
MVP		0.60
MPC		0.17
ClinPred		0.64	D
GERP RS		3.0
Varity_R		0.35
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs761931528; hg19: chr17-10210305;