rs2277644

Positions:

• chr17-10328100-C-A
• chr17-10328100-C-G
• chr17-10328100-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003802.3(MYH13):​c.2457G>T​(p.Gln819His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728

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]

(HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH13	NM_003802.3	c.2457G>T	p.Gln819His	missense_variant	22/41	ENST00000252172.9
LOC107985004	XR_007065617.1	n.681+7588C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH13	ENST00000252172.9	c.2457G>T	p.Gln819His	missense_variant	22/41	1	NM_003802.3	P1
MYH13	ENST00000621918.1	c.2457G>T	p.Gln819His	missense_variant	20/39	1		P1
	ENST00000577743.1	n.246+3133C>A		intron_variant, non_coding_transcript_variant		2
MYH13	ENST00000418404.8	c.2457G>T	p.Gln819His	missense_variant	21/40	5		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;D;D
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	.;D;.
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Pathogenic	4.0	H;H;H
MutationTaster	Benign	0.038	P;P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.1	.;.;D
REVEL	Pathogenic	0.75
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.95
MutPred		0.80		Loss of MoRF binding (P = 0.0912);Loss of MoRF binding (P = 0.0912);Loss of MoRF binding (P = 0.0912);
MVP		0.89
MPC		0.38
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.53
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: -31

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277644; hg19: chr17-10231417;