chr17-32654575-G-A

Variant names:

• chr17-32654575-G-A
• rs146175770
• NM_015194.3:c.2392C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015194.3(MYO1D):​c.2392C>T​(p.Pro798Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000867 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: MYO1D NM_015194.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• 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]

MYO1D-AS1 (HGNC:58309):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06253129).

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.2392C>T	p.Pro798Ser	missense	Exon 18 of 22	NP_056009.1	O94832
	MYO1D	NM_001303279.2		c.2392C>T	p.Pro798Ser	missense	Exon 18 of 22	NP_001290208.1	J3QRN6
	MYO1D	NM_001411088.1		c.2128C>T	p.Pro710Ser	missense	Exon 19 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.2392C>T	p.Pro798Ser	missense	Exon 18 of 22	ENSP00000324527.5	O94832
	MYO1D	ENST00000889850.1		c.2449C>T	p.Pro817Ser	missense	Exon 19 of 23	ENSP00000559909.1
	MYO1D	ENST00000889848.1		c.2440C>T	p.Pro814Ser	missense	Exon 19 of 23	ENSP00000559907.1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000957 AC: 24 AN: 250900 AF XY: 0.0000664

Gnomad AFR exome AF: 0.00142

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: 0.0000458 AC: 67 AN: 1461524 Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31 AN XY: 727046

African (AFR) AF: 0.00173 AC: 58 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111848

Other (OTH) AF: 0.0000994 AC: 6 AN: 60384

GnomAD4 genome AF: 0.000479 AC: 73 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74502

African (AFR) AF: 0.00173 AC: 72 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000309 Hom.: 0

Bravo AF: 0.000506

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

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	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.063	T
MetaSVM	Uncertain	0.022	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.6
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.013	D
Sift4G	Benign	0.48	T
Polyphen		0.13	B
Vest4		0.17
MVP		0.90
MPC		0.31
ClinPred		0.089	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.40
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs146175770; hg19: chr17-30981593;