Genetic Variant MYO5B:c.2004-15_2004-13dupTTT (chr18-49929610-G-GAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001080467.3(MYO5B):c.2004-15_2004-13dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

MYO5B
NM_001080467.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.06

Publications

2 publications found

Variant links:

Genes affected

MYO5B (HGNC:7603): (myosin VB) The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

MYO5B Gene-Disease associations (from GenCC):

microvillus inclusion disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
cholestasis, progressive familial intrahepatic, 10
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
progressive familial intrahepatic cholestasis type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.2004-15_2004-13dupTTT		intron_variant	Intron 16 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12 link	c.2004-13_2004-12insTTT		intron_variant	Intron 16 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1 link	c.1800-13_1800-12insTTT		intron_variant	Intron 14 of 37			ENSP00000513188.1

Frequencies

GnomAD3 genomes

AF:

0.0000301

AC:

AN:

132862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00352

Gnomad NFE

AF:

0.0000480

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000415

AC:

479

AN:

1155242

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

246

AN XY:

577444

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000376

AC:

AN:

26604

American (AMR)

AF:

0.00

AC:

AN:

32068

Ashkenazi Jewish (ASJ)

AF:

0.000450

AC:

AN:

22232

East Asian (EAS)

AF:

0.00

AC:

AN:

33536

South Asian (SAS)

AF:

0.000569

AC:

AN:

70330

European-Finnish (FIN)

AF:

0.000193

AC:

AN:

36180

Middle Eastern (MID)

AF:

0.000284

AC:

AN:

3520

European-Non Finnish (NFE)

AF:

0.000462

AC:

407

AN:

881738

Other (OTH)

AF:

0.000265

AC:

AN:

49034

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.313

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000226

AC:

AN:

132840

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

63450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35466

American (AMR)

AF:

0.00

AC:

AN:

13142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3244

East Asian (EAS)

AF:

0.00

AC:

AN:

4606

South Asian (SAS)

AF:

0.00

AC:

AN:

4060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000480

AC:

AN:

62520

Other (OTH)

AF:

0.00

AC:

AN:

1816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

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

Publications

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18-49929610-GAAAAAAA-GAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over