Variant 2-191392172-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_001130158.3(MYO1B):c.2047T>A(p.Ser683Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000814 in 1,607,482 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 2 hom. )

Consequence

MYO1B
NM_001130158.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65

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 Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, MYO1B

BP4

Computational evidence support a benign effect (MetaRNN=0.033437252).

BS2

High AC in GnomAd at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1B	NM_001130158.3 linkuse as main transcript	c.2047T>A	p.Ser683Thr	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.2047T>A	p.Ser683Thr	missense_variant	19/31	1	NM_001130158.3	P1	O43795-1
MYO1B	ENST00000304164.8 linkuse as main transcript	c.2047T>A	p.Ser683Thr	missense_variant	19/31	1		P1	O43795-1
MYO1B	ENST00000339514.8 linkuse as main transcript	c.2047T>A	p.Ser683Thr	missense_variant	19/29	1			O43795-2
MYO1B	ENST00000392316.5 linkuse as main transcript	c.2047T>A	p.Ser683Thr	missense_variant	18/29	5

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000661

AC:

166

AN:

251240

Hom.:

AF XY:

0.000677

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000829

AC:

1206

AN:

1455144

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

598

AN XY:

723384

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000903

Gnomad4 NFE exome

AF:

0.000992

Gnomad4 OTH exome

AF:

0.000582

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152338

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000936

Hom.:

Bravo

AF:

0.000601

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000601

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

Oct 22, 2021

The c.2047T>A (p.S683T) alteration is located in exon 19 (coding exon 18) of the MYO1B gene. This alteration results from a T to A substitution at nucleotide position 2047, causing the serine (S) at amino acid position 683 to be replaced by a threonine (T). 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

Benign

0.083

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Benign

0.38

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;.;D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

-1.5

N;N;N;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.81

N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.015

B;B;B;.

Vest4

0.49

MVP

0.51

MPC

0.42

ClinPred

0.035

GERP RS

5.7

Varity_R

0.10

gMVP

0.77

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