rs1131692247

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM1PM2PP2PP3PP5

The NM_001080483.3(MYMK):c.553T>C(p.Cys185Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

MYMK
NM_001080483.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.58

Publications

4 publications found

Variant links:

Genes affected

MYMK (HGNC:33778): (myomaker, myoblast fusion factor) Involved in myoblast fusion. Located in plasma membrane. Implicated in Carey-Fineman-Ziter syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MYMK Gene-Disease associations (from GenCC):

Carey-Fineman-Ziter syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, ClinGen, Illumina
Carey-Fineman-Ziter syndrome 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

MYMK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM1

In a chain Protein myomaker (size 220) in uniprot entity MYMK_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_001080483.3

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 5 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.76146 (below the threshold of 3.09). Trascript score misZ: 1.1389 (below the threshold of 3.09). GenCC associations: The gene is linked to Carey-Fineman-Ziter syndrome 1, Carey-Fineman-Ziter syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.756

PP5

Variant 9-133514749-A-G is Pathogenic according to our data. Variant chr9-133514749-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 430840.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYMK	NM_001080483.3 link	c.553T>C	p.Cys185Arg	missense_variant	Exon 5 of 5	ENST00000339996.4	NP_001073952.1	A6NI61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYMK	ENST00000339996.4 link	c.553T>C	p.Cys185Arg	missense_variant	Exon 5 of 5	2	NM_001080483.3	ENSP00000419712.2		A6NI61

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251148

AF XY:

0.00

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111908

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Congenital nonprogressive myopathy with Moebius and Robin sequences

Pathogenic:1

Jan 07, 2019

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

Eigen

Benign

0.092

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.84

M_CAP

Benign

0.060

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.93

PhyloP100

4.6

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.3

REVEL

Benign

0.19

Sift

Uncertain

0.011

Sift4G

Uncertain

0.0060

Polyphen

0.60

Vest4

0.68

MutPred

0.70

Loss of catalytic residue at C185 (P = 0.0915);

MVP

0.45

MPC

0.83

ClinPred

0.85

GERP RS

3.8

Varity_R

0.62

gMVP

0.79

Mutation Taster

=21/79

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over