rs141895982

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077365.2(POMT1):c.2067C>A(p.His689Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,608,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H689R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

POMT1
NM_001077365.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: -0.128

Publications

0 publications found

Variant links:

Genes affected

POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

POMT1 Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp, G2P
myopathy caused by variation in POMT1
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive limb-girdle muscular dystrophy type 2K
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23762041).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077365.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POMT1	NM_001077365.2	MANE Select	c.2067C>A	p.His689Gln	missense	Exon 20 of 20	NP_001070833.1	A0A140VKE0
POMT1	NM_001353193.2		c.2133C>A	p.His711Gln	missense	Exon 20 of 20	NP_001340122.2	Q9Y6A1-1
POMT1	NM_007171.4		c.2133C>A	p.His711Gln	missense	Exon 20 of 20	NP_009102.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POMT1	ENST00000402686.8	TSL:1 MANE Select	c.2067C>A	p.His689Gln	missense	Exon 20 of 20	ENSP00000385797.4	Q9Y6A1-2
POMT1	ENST00000372228.9	TSL:1	c.2133C>A	p.His711Gln	missense	Exon 20 of 20	ENSP00000361302.3	Q9Y6A1-1
POMT1	ENST00000423007.6	TSL:1	c.2124C>A	p.His708Gln	missense	Exon 19 of 19	ENSP00000404119.2	A0A1V1FTP4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000816

AC:

AN:

245152

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455976

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33374

American (AMR)

AF:

0.0000225

AC:

AN:

44408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

85490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4164

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110916

Other (OTH)

AF:

0.0000166

AC:

AN:

60138

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

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive limb-girdle muscular dystrophy type 2K (1)

Inborn genetic diseases (1)

Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.0037

BayesDel_noAF

Benign

-0.16

CADD

Benign

3.5

(source)

DANN

Benign

0.83

DEOGEN2

Uncertain

0.68

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.9

PhyloP100

-0.13

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.43

Sift

Benign

0.17

Sift4G

Benign

0.16

Polyphen

0.63

Vest4

0.34

MutPred

0.48

Loss of helix (P = 0.1706)

MVP

0.85

MPC

0.41

ClinPred

0.15

GERP RS

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.25

Mutation Taster

=93/7

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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