NM_001145809.2:c.3033+11T>C

Variant names:

Variant summary

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

The NM_001145809.2(MYH14):c.3033+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,555,034 control chromosomes in the GnomAD database, including 594,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57768 hom., cov: 33)

Exomes 𝑓: 0.87 ( 536789 hom. )

Consequence

MYH14
NM_001145809.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.209

Publications

12 publications found

Variant links:

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH14 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 4A
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH14 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 (BayesDel_noAF=-0.9).

BP6

Variant 19-50268378-T-C is Benign according to our data. Variant chr19-50268378-T-C is described in ClinVar as Benign. ClinVar VariationId is 44063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH14	NM_001145809.2	MANE Select	c.3033+11T>C	intron	N/A	NP_001139281.1	Q7Z406-2
MYH14	NM_001077186.2		c.2934+11T>C	intron	N/A	NP_001070654.1	Q7Z406-6
MYH14	NM_024729.4		c.2910+11T>C	intron	N/A	NP_079005.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH14	ENST00000642316.2	MANE Select	c.3033+11T>C	intron	N/A	ENSP00000493594.1	Q7Z406-2
MYH14	ENST00000599920.5	TSL:1	c.2934+11T>C	intron	N/A	ENSP00000469573.1	M0QY43
MYH14	ENST00000425460.6	TSL:5	c.2934+11T>C	intron	N/A	ENSP00000407879.1	Q7Z406-6

Frequencies

GnomAD3 genomes

AF:

0.871

AC:

132493

AN:

152154

Hom.:

57727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.857

Gnomad AMI

AF:

0.838

Gnomad AMR

AF:

0.884

Gnomad ASJ

AF:

0.868

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.886

Gnomad FIN

AF:

0.907

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.871

Gnomad OTH

AF:

0.853

GnomAD2 exomes

AF:

0.879

AC:

141371

AN:

160754

AF XY:

0.878

show subpopulations

Gnomad AFR exome

AF:

0.858

Gnomad AMR exome

AF:

0.913

Gnomad ASJ exome

AF:

0.857

Gnomad EAS exome

AF:

0.849

Gnomad FIN exome

AF:

0.902

Gnomad NFE exome

AF:

0.871

Gnomad OTH exome

AF:

0.874

GnomAD4 exome

AF:

0.875

AC:

1227108

AN:

1402762

Hom.:

536789

Cov.:

AF XY:

0.875

AC XY:

605809

AN XY:

692456

show subpopulations

African (AFR)

AF:

0.852

AC:

27110

AN:

31812

American (AMR)

AF:

0.907

AC:

33044

AN:

36440

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

21655

AN:

25210

East Asian (EAS)

AF:

0.876

AC:

31613

AN:

36088

South Asian (SAS)

AF:

0.885

AC:

70339

AN:

79462

European-Finnish (FIN)

AF:

0.901

AC:

42769

AN:

47450

Middle Eastern (MID)

AF:

0.869

AC:

4798

AN:

5520

European-Non Finnish (NFE)

AF:

0.873

AC:

944936

AN:

1082532

Other (OTH)

AF:

0.873

AC:

50844

AN:

58248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

7404

14808

22211

29615

37019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20976

41952

62928

83904

104880

<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:

0.871

AC:

132587

AN:

152272

Hom.:

57768

Cov.:

AF XY:

0.872

AC XY:

64952

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.857

AC:

35635

AN:

41560

American (AMR)

AF:

0.884

AC:

13516

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

3011

AN:

3470

East Asian (EAS)

AF:

0.857

AC:

4431

AN:

5172

South Asian (SAS)

AF:

0.886

AC:

4273

AN:

4824

European-Finnish (FIN)

AF:

0.907

AC:

9631

AN:

10620

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.871

AC:

59272

AN:

68014

Other (OTH)

AF:

0.853

AC:

1804

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

925

1849

2774

3698

4623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.870

Hom.:

104836

Bravo

AF:

0.870

Asia WGS

AF:

0.880

AC:

3060

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Autosomal dominant nonsyndromic hearing loss 4A (2)

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.8

(source)

DANN

Benign

0.60

PhyloP100

-0.21

Mutation Taster

=21/79

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over