17-10307064-T-C

Position:

• chr17-10307064-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003802.3(MYH13):​c.5170A>G​(p.Asn1724Asp) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH13 NM_003802.3 missense, splice_region
• Scores: Splicing: ADA: 0.3392
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.23

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH13	NM_003802.3	c.5170A>G	p.Asn1724Asp	missense_variant, splice_region_variant	36/41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_007065617.1	n.96-10434T>C		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3	n.96-10434T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.5170A>G	p.Asn1724Asp	missense_variant, splice_region_variant	36/41	1	NM_003802.3	ENSP00000252172	P1
MYH13	ENST00000621918.1	c.5170A>G	p.Asn1724Asp	missense_variant, splice_region_variant	34/39	1		ENSP00000480864	P1
	ENST00000609088.1	n.95-10434T>C		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8	c.5170A>G	p.Asn1724Asp	missense_variant, splice_region_variant	35/40	5		ENSP00000404570	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

May 28, 2024

The c.5170A>G (p.N1724D) alteration is located in exon 36 (coding exon 34) of the MYH13 gene. This alteration results from a A to G substitution at nucleotide position 5170, causing the asparagine (N) at amino acid position 1724 to be replaced by an aspartic acid (D). 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	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	.;D;.
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Pathogenic	4.2	H;H;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	.;.;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	.;.;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.67
MutPred		0.71		Loss of MoRF binding (P = 0.0572);Loss of MoRF binding (P = 0.0572);Loss of MoRF binding (P = 0.0572);
MVP		0.88
MPC		0.23
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.64
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.34
dbscSNV1_RF	Benign	0.58
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: chr17-10210381;