chr17-32494773-C-A

Variant names:

• chr17-32494773-C-A
• NM_015194.3:c.3007G>T
• MYO1D p.Val1003Leu

Variant summary

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

The NM_015194.3(MYO1D):​c.3007G>T​(p.Val1003Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1003M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO1D NM_015194.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40
• Publications: 0 publications found

Genes affected

MYO1D (HGNC:7598): (myosin ID) Enables protein domain specific binding activity. Predicted to be involved in actin filament organization; early endosome to recycling endosome transport; and vesicle transport along actin filament. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015194.3. 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
	MYO1D	NM_015194.3	MANE Select	c.3007G>T	p.Val1003Leu	missense	Exon 22 of 22	NP_056009.1	O94832
	MYO1D	NM_001411088.1		c.2743G>T	p.Val915Leu	missense	Exon 23 of 23	NP_001398017.1	K7EIG7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1D	ENST00000318217.10	TSL:1 MANE Select	c.3007G>T	p.Val1003Leu	missense	Exon 22 of 22	ENSP00000324527.5	O94832
	MYO1D	ENST00000889850.1		c.3064G>T	p.Val1022Leu	missense	Exon 23 of 23	ENSP00000559909.1
	MYO1D	ENST00000889848.1		c.3055G>T	p.Val1019Leu	missense	Exon 23 of 23	ENSP00000559907.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.0058	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T
Eigen	Benign	0.0087
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.23
Sift	Benign	0.35	T
Sift4G	Benign	0.45	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.19

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

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

Other links and lift over

hg19: chr17-30821791;