NM_015194.3:c.2312G>A

Variant names:

• chr17-32659148-C-T
• rs7215958
• NM_015194.3:c.2312G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015194.3(MYO1D):​c.2312G>A​(p.Arg771His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,614,176 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (123 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (126 hom.)
• Consequence: MYO1D NM_015194.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10
• Publications: 11 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021068454).
• BP6: Variant 17-32659148-C-T is Benign according to our data. Variant chr17-32659148-C-T is described in ClinVar as Benign. ClinVar VariationId is 781363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0706 is higher than 0.05.

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.2312G>A	p.Arg771His	missense	Exon 17 of 22	NP_056009.1	O94832
	MYO1D	NM_001303279.2		c.2312G>A	p.Arg771His	missense	Exon 17 of 22	NP_001290208.1	J3QRN6
	MYO1D	NM_001411088.1		c.2048G>A	p.Arg683His	missense	Exon 18 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.2312G>A	p.Arg771His	missense	Exon 17 of 22	ENSP00000324527.5	O94832
	MYO1D	ENST00000889850.1		c.2369G>A	p.Arg790His	missense	Exon 18 of 23	ENSP00000559909.1
	MYO1D	ENST00000889848.1		c.2360G>A	p.Arg787His	missense	Exon 18 of 23	ENSP00000559907.1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3283 AN: 152176 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00723 AC: 1818 AN: 251282 AF XY: 0.00618

Gnomad AFR exome AF: 0.0757

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00173

Gnomad OTH exome AF: 0.00635

GnomAD4 exome AF: 0.00350 AC: 5115 AN: 1461882 Hom.: 126 Cov.: 30 AF XY: 0.00349 AC XY: 2537 AN XY: 727246

African (AFR) AF: 0.0749 AC: 2508 AN: 33478

American (AMR) AF: 0.00481 AC: 215 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000803 AC: 21 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00624 AC: 538 AN: 86258

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53418

Middle Eastern (MID) AF: 0.0260 AC: 150 AN: 5766

European-Non Finnish (NFE) AF: 0.00114 AC: 1270 AN: 1112006

Other (OTH) AF: 0.00657 AC: 397 AN: 60396

GnomAD4 genome AF: 0.0217 AC: 3301 AN: 152294 Hom.: 123 Cov.: 32 AF XY: 0.0210 AC XY: 1567 AN XY: 74472

African (AFR) AF: 0.0727 AC: 3021 AN: 41540

American (AMR) AF: 0.00660 AC: 101 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4824

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 68036

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.00855 Hom.: 144

Bravo AF: 0.0245

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0679 AC: 299

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.00853 AC: 1036

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.00240

EpiControl AF: 0.00243

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.30
Sift	Benign	0.23	T
Sift4G	Benign	0.14	T
Polyphen		0.94	P
Vest4		0.19
MVP		0.83
MPC		0.34
ClinPred		0.0082	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.030
gMVP		0.43
Mutation Taster		=98/2	polymorphism (auto)

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: rs7215958; hg19: chr17-30986166;