12-109445569-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001101421.4(MYO1H):c.3050T>C(p.Leu1017Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,610,944 control chromosomes in the GnomAD database, including 347,915 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 40130 hom., cov: 32)

Exomes 𝑓: 0.65 ( 307785 hom. )

Consequence

MYO1H
NM_001101421.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0330

Publications

45 publications found

Variant links:

Genes affected

MYO1H (HGNC:13879): (myosin IH) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

MYO1H Gene-Disease associations (from GenCC):

congenital central hypoventilation syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
central hypoventilation syndrome, congenital, 2, and autonomic dysfunction
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MYO1H links:

ENSG00000255655 (HGNC:):

ENSG00000255655 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.0434917E-7).

BP6

Variant 12-109445569-T-C is Benign according to our data. Variant chr12-109445569-T-C is described in ClinVar as Benign. ClinVar VariationId is 1267555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MYO1H	NM_001101421.4 link	c.3050T>C	p.Leu1017Pro	missense_variant	Exon 31 of 32	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3 link	c.3068T>C	p.Leu1023Pro	missense_variant	Exon 33 of 34		XP_011536525.1
MYO1H	XM_047428738.1 link	c.3002T>C	p.Leu1001Pro	missense_variant	Exon 30 of 31		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MYO1H	ENST00000310903.10 link	c.3050T>C	p.Leu1017Pro	missense_variant	Exon 31 of 32	5	NM_001101421.4	ENSP00000439182.2
ENSG00000255655	ENST00000539987.1 link	n.444A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
MYO1H	ENST00000542268.5 link	n.850T>C		non_coding_transcript_exon_variant	Exon 8 of 9	2
MYO1H	ENST00000543960.1 link	n.314T>C		non_coding_transcript_exon_variant	Exon 4 of 6	4		ENSP00000474025.1

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108166

AN:

151982

Hom.:

40072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.931

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.692

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.700

GnomAD2 exomes

AF:

0.644

AC:

159137

AN:

247116

AF XY:

0.649

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.528

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.645

AC:

941597

AN:

1458844

Hom.:

307785

Cov.:

AF XY:

0.648

AC XY:

470419

AN XY:

725596

show subpopulations

African (AFR)

AF:

0.943

AC:

31496

AN:

33396

American (AMR)

AF:

0.542

AC:

24048

AN:

44378

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

17595

AN:

26086

East Asian (EAS)

AF:

0.473

AC:

18760

AN:

39620

South Asian (SAS)

AF:

0.711

AC:

60854

AN:

85618

European-Finnish (FIN)

AF:

0.558

AC:

29680

AN:

53212

Middle Eastern (MID)

AF:

0.750

AC:

4323

AN:

5762

European-Non Finnish (NFE)

AF:

0.644

AC:

715478

AN:

1110518

Other (OTH)

AF:

0.653

AC:

39363

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

15642

31285

46927

62570

78212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18804

37608

56412

75216

94020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.712

AC:

108281

AN:

152100

Hom.:

40130

Cov.:

AF XY:

0.702

AC XY:

52156

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.931

AC:

38660

AN:

41536

American (AMR)

AF:

0.591

AC:

9031

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

2338

AN:

3470

East Asian (EAS)

AF:

0.502

AC:

2600

AN:

5184

South Asian (SAS)

AF:

0.692

AC:

3325

AN:

4808

European-Finnish (FIN)

AF:

0.550

AC:

5796

AN:

10538

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.650

AC:

44188

AN:

67974

Other (OTH)

AF:

0.700

AC:

1476

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1457

2914

4370

5827

7284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.666

Hom.:

146398

Bravo

AF:

0.724

TwinsUK

AF:

0.646

AC:

2395

ALSPAC

AF:

0.633

AC:

2441

ESP6500AA

AF:

0.920

AC:

3399

ESP6500EA

AF:

0.644

AC:

5268

ExAC

AF:

0.658

AC:

79488

Asia WGS

AF:

0.606

AC:

2107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29986156) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.62

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.0071

T;T

MetaRNN

Benign

6.0e-7

T;T

MetaSVM

Benign

-0.99

PhyloP100

0.033

PrimateAI

Benign

0.28

REVEL

Benign

0.030

Sift4G

Benign

0.43

T;T

Vest4

0.028

MPC

0.13

ClinPred

0.00085

GERP RS

2.8

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over