3-108383603-C-G

Position:

• chr3-108383603-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014981.3(MYH15):​c.5758G>C​(p.Gly1920Arg) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH15 NM_014981.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0360

Genes affected

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900545 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09467071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH15	NM_014981.3	c.5758G>C	p.Gly1920Arg	missense_variant	40/41	ENST00000693548.1	NP_055796.2
LOC124900545	XR_007095998.1	n.112+1952C>G		intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3	c.5818G>C	p.Gly1940Arg	missense_variant	42/43		XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH15	ENST00000693548.1	c.5758G>C	p.Gly1920Arg	missense_variant	40/41		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5	c.5758G>C	p.Gly1920Arg	missense_variant	41/42	1		ENSP00000273353	P1
MYH15	ENST00000689784.1	c.4777G>C	p.Gly1593Arg	missense_variant	32/33			ENSP00000509841

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 14, 2021

The c.5818G>C (p.G1940R) alteration is located in exon 41 (coding exon 41) of the MYH15 gene. This alteration results from a G to C substitution at nucleotide position 5818, causing the glycine (G) at amino acid position 1940 to be replaced by an arginine (R). 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	Benign	0.090
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Benign	0.055	T
Sift4G	Uncertain	0.047	D
Polyphen		0.024	B
Vest4		0.071
MutPred		0.22		Gain of methylation at K1941 (P = 0.1291);
MVP		0.75
MPC		0.098
ClinPred		0.17	T
GERP RS		3.5
Varity_R		0.15
gMVP		0.087

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: chr3-108102450; COSMIC: COSV56313210;