17-10303257-T-A

Variant summary

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

The NM_003802.3(MYH13):c.5606A>T(p.Gln1869Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYH13 NM_003802.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.93

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH13	NM_003802.3	c.5606A>T	p.Gln1869Leu	missense_variant	39/41	ENST00000252172.9
LOC107985004	XR_007065617.1	n.95+11344T>A		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3	n.95+11344T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH13	ENST00000252172.9	c.5606A>T	p.Gln1869Leu	missense_variant	39/41	1	NM_003802.3	P1
MYH13	ENST00000621918.1	c.5606A>T	p.Gln1869Leu	missense_variant	37/39	1		P1
	ENST00000609088.1	n.94+11344T>A		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8	c.5606A>T	p.Gln1869Leu	missense_variant	38/40	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461570 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727094

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.5606A>T (p.Q1869L) alteration is located in exon 39 (coding exon 37) of the MYH13 gene. This alteration results from a A to T substitution at nucleotide position 5606, causing the glutamine (Q) at amino acid position 1869 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Pathogenic	4.3	H;H;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.57	T
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.76	P;P;P
Vest4		0.73
MutPred		0.58		Loss of disorder (P = 0.0517);Loss of disorder (P = 0.0517);Loss of disorder (P = 0.0517);
MVP		0.87
MPC		0.49
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.68
gMVP		0.26

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: chr17-10206574;