Genetic Variant MYO15B:p.Pro2802Pro (chr17-75624408-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001395058.1(MYO15B):c.8406G>C(p.Pro2802Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000997 in 702,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P2802P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

MYO15B
NM_001395058.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.84

Publications

0 publications found

Variant links:

Genes affected

MYO15B (HGNC:14083): (myosin XVB) Predicted to enable ATP binding activity; actin binding activity; and cytoskeletal motor activity. Predicted to be located in brush border; cytoplasm; and cytoskeleton. Predicted to be part of myosin complex. [provided by Alliance of Genome Resources, Apr 2022]

MYO15B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-6.84 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395058.1. 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
	MYO15B	NM_001395058.1	MANE Select	c.8406G>C	p.Pro2802Pro	synonymous	Exon 57 of 64	NP_001381987.1	Q96JP2-1
	MYO15B	NM_001309242.2		c.8292G>C	p.Pro2764Pro	synonymous	Exon 56 of 63	NP_001296171.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYO15B	ENST00000645453.3	MANE Select	c.8406G>C	p.Pro2802Pro	synonymous	Exon 57 of 64	ENSP00000495242.3	Q96JP2-1
MYO15B	ENST00000578220.5	TSL:3	c.570G>C	p.Pro190Pro	synonymous	Exon 8 of 10	ENSP00000487752.1	A0A0J9YW04
MYO15B	ENST00000642007.2		c.3925-135G>C		intron	N/A	ENSP00000492911.2	A0A286YF23

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152154

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:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000144

AC:

AN:

139144

AF XY:

0.0000132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000909

AC:

AN:

550160

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

297836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15806

American (AMR)

AF:

0.00

AC:

AN:

34712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20028

East Asian (EAS)

AF:

0.0000312

AC:

AN:

32102

South Asian (SAS)

AF:

0.00

AC:

AN:

62306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

316950

Other (OTH)

AF:

0.00

AC:

AN:

30622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.010

(source)

DANN

Benign

0.69

PhyloP100

-6.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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