Genetic Variant MYO5B:c.*3273G>A (chr18-49823198-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001080467.3(MYO5B):c.*3273G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 140,498 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 18 hom., cov: 38)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYO5B
NM_001080467.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.479

Publications

1 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 links:

ENSG00000266997 (HGNC:):

ENSG00000266997 links:

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

SNHG22 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=-0.92).

BP6

Variant 18-49823198-C-T is Benign according to our data. Variant chr18-49823198-C-T is described in ClinVar as Benign. ClinVar VariationId is 326925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080467.3. 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
	MYO5B	NM_001080467.3	MANE Select	c.*3273G>A		3_prime_UTR	Exon 40 of 40	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.40+9136C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.*3273G>A	3_prime_UTR	Exon 40 of 40	ENSP00000285039.6	Q9ULV0-1
ENSG00000266997	ENST00000590532.2	TSL:5	n.*35+3238G>A	intron	N/A	ENSP00000467396.2	K7EPI3
MYO5B	ENST00000697219.1		c.*3273G>A	3_prime_UTR	Exon 38 of 38	ENSP00000513188.1	A0A8V8TM52

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3446

AN:

140372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00809

Gnomad EAS

AF:

0.00564

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.00290

Gnomad MID

AF:

0.0203

Gnomad NFE

AF:

0.00367

Gnomad OTH

AF:

0.0160

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0246

AC:

3453

AN:

140498

Hom.:

Cov.:

AF XY:

0.0265

AC XY:

1814

AN XY:

68382

show subpopulations

African (AFR)

AF:

0.0635

AC:

2424

AN:

38190

American (AMR)

AF:

0.0121

AC:

168

AN:

13922

Ashkenazi Jewish (ASJ)

AF:

0.00809

AC:

AN:

3214

East Asian (EAS)

AF:

0.00565

AC:

AN:

4776

South Asian (SAS)

AF:

0.116

AC:

512

AN:

4426

European-Finnish (FIN)

AF:

0.00290

AC:

AN:

9670

Middle Eastern (MID)

AF:

0.0216

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00367

AC:

232

AN:

63270

Other (OTH)

AF:

0.0158

AC:

AN:

1896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

174

347

521

694

868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0373

Hom.:

Bravo

AF:

0.0244

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital microvillous atrophy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

DANN

Benign

0.29

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over