Variant 2-191392161-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001130158.3(MYO1B):c.2036C>T(p.Ser679Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MYO1B
NM_001130158.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

MYO1B (HGNC:7596): (myosin IB) Enables ATP binding activity; actin filament binding activity; and microfilament motor activity. Involved in actin filament organization and post-Golgi vesicle-mediated transport. Located in several cellular components, including actin filament; endosome; and perinuclear region of cytoplasm. Colocalizes with trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

MYO1B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, MYO1B

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1B	NM_001130158.3 linkuse as main transcript	c.2036C>T	p.Ser679Phe	missense_variant	19/31	ENST00000392318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1B	ENST00000392318.8 linkuse as main transcript	c.2036C>T	p.Ser679Phe	missense_variant	19/31	1	NM_001130158.3	P1	O43795-1
MYO1B	ENST00000304164.8 linkuse as main transcript	c.2036C>T	p.Ser679Phe	missense_variant	19/31	1		P1	O43795-1
MYO1B	ENST00000339514.8 linkuse as main transcript	c.2036C>T	p.Ser679Phe	missense_variant	19/29	1			O43795-2
MYO1B	ENST00000392316.5 linkuse as main transcript	c.2036C>T	p.Ser679Phe	missense_variant	18/29	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251218

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135860

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1456698

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000632

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

The c.2036C>T (p.S679F) alteration is located in exon 19 (coding exon 18) of the MYO1B gene. This alteration results from a C to T substitution at nucleotide position 2036, causing the serine (S) at amino acid position 679 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;.;D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

0.69

N;N;N;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.8

D;D;D;D

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

0.82

P;P;P;.

Vest4

0.61

MutPred

0.50

Loss of phosphorylation at S679 (P = 0.038);Loss of phosphorylation at S679 (P = 0.038);Loss of phosphorylation at S679 (P = 0.038);Loss of phosphorylation at S679 (P = 0.038);

MVP

0.67

MPC

1.1

ClinPred

0.92

GERP RS

5.7

Varity_R

0.55

gMVP

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over