3-108428880-G-C

Variant names:

• chr3-108428880-G-C
• NM_014981.3:c.3314C>G
• MYH15 p.Thr1105Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014981.3(MYH15):​c.3314C>G​(p.Thr1105Ser) variant causes a missense, splice region 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. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYH15 NM_014981.3 missense, splice_region
• Scores: Splicing: ADA: 0.0002772
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098270476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014981.3. 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
	MYH15	NM_014981.3	MANE Select	c.3314C>G	p.Thr1105Ser	missense splice_region	Exon 27 of 41	NP_055796.2	A0A8I5KXJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH15	ENST00000693548.1	MANE Select	c.3314C>G	p.Thr1105Ser	missense splice_region	Exon 27 of 41	ENSP00000508967.1	Q9Y2K3
	MYH15	ENST00000273353.5	TSL:1	c.3314C>G	p.Thr1105Ser	missense splice_region	Exon 28 of 42	ENSP00000273353.4	Q9Y2K3
	MYH15	ENST00000689784.1		c.2333C>G	p.Thr778Ser	missense splice_region	Exon 19 of 33	ENSP00000509841.1	A0A8I5KYE8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.7
DANN	Benign	0.95
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.71
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.99	L
PhyloP100		1.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Benign	0.23	T
Varity_R		0.048
gMVP		0.040
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.018
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-108147727;