17-32494773-C-T

Variant names:

• chr17-32494773-C-T
• rs377477685
• NM_015194.3:c.3007G>A

Variant summary

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

The NM_015194.3(MYO1D):​c.3007G>A​(p.Val1003Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,606,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MYO1D NM_015194.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40
• Publications: 1 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>A	p.Val1003Met	missense	Exon 22 of 22	NP_056009.1	O94832
	MYO1D	NM_001411088.1		c.2743G>A	p.Val915Met	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>A	p.Val1003Met	missense	Exon 22 of 22	ENSP00000324527.5	O94832
	MYO1D	ENST00000889850.1		c.3064G>A	p.Val1022Met	missense	Exon 23 of 23	ENSP00000559909.1
	MYO1D	ENST00000889848.1		c.3055G>A	p.Val1019Met	missense	Exon 23 of 23	ENSP00000559907.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000422 AC: 1 AN: 236708 AF XY: 0.00

Gnomad AFR exome AF: 0.0000676

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1454174 Hom.: 0 Cov.: 30 AF XY: 0.00000692 AC XY: 5 AN XY: 722976

African (AFR) AF: 0.0000902 AC: 3 AN: 33254

American (AMR) AF: 0.00 AC: 0 AN: 43716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25894

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39234

South Asian (SAS) AF: 0.00 AC: 0 AN: 85166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108662

Other (OTH) AF: 0.0000166 AC: 1 AN: 60102

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152134 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.0000966 AC: 4 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.35	N
REVEL	Uncertain	0.34
Sift	Benign	0.065	T
Sift4G	Benign	0.094	T
Polyphen		1.0	D
Vest4		0.53
MVP		0.48
MPC		0.83
ClinPred		0.66	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.21
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs377477685; hg19: chr17-30821791; COSMIC: COSV57830982; COSMIC: COSV57830982;