17-32659167-G-A

Position:

• chr17-32659167-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015194.3(MYO1D):​c.2293C>T​(p.Pro765Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,614,138 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (19 hom.)
• Consequence: MYO1D NM_015194.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.97

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008619487).
• BP6: Variant 17-32659167-G-A is Benign according to our data. Variant chr17-32659167-G-A is described in ClinVar as [Benign]. Clinvar id is 710462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00164 (2398/1461892) while in subpopulation MID AF= 0.0232 (134/5766). AF 95% confidence interval is 0.02. There are 19 homozygotes in gnomad4_exome. There are 1331 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1D	NM_015194.3	c.2293C>T	p.Pro765Ser	missense_variant	17/22	ENST00000318217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1D	ENST00000318217.10	c.2293C>T	p.Pro765Ser	missense_variant	17/22	1	NM_015194.3	P1
	ENST00000582272.1	n.141+26688G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 616 AN: 152128 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00244 AC: 613 AN: 251422 Hom.: 7 AF XY: 0.00262 AC XY: 356 AN XY: 135896

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00568

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00146

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00164 AC: 2398 AN: 1461892 Hom.: 19 Cov.: 30 AF XY: 0.00183 AC XY: 1331 AN XY: 727246

Gnomad4 AFR exome AF: 0.0136

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.000803

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00601

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000936

Gnomad4 OTH exome AF: 0.00286

GnomAD4 genome AF: 0.00404 AC: 615 AN: 152246 Hom.: 3 Cov.: 33 AF XY: 0.00403 AC XY: 300 AN XY: 74444

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00128

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00222 Hom.: 7

Bravo AF: 0.00490

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0136 AC: 60

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.00276 AC: 335

Asia WGS AF: 0.00693 AC: 26 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	MYO1D: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D
MetaRNN	Benign	0.0086	T;T;T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.8	D;.;.
REVEL	Uncertain	0.55
Sift	Benign	0.13	T;.;.
Sift4G	Benign	0.21	T;T;T
Polyphen		0.78	P;.;.
Vest4		0.55
MVP		0.93
MPC		0.43
ClinPred		0.039	T
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.17
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs7209106; hg19: chr17-30986185;