rs1131692248

Variant names:

• chr9-133524843-A-T
• rs1131692248
• NM_001080483.3:c.2T>A

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_001080483.3(MYMK):​c.2T>A​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: MYMK NM_001080483.3 start_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.13
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 32 codons. Genomic position: 133524751. Lost 0.141 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-133524843-A-T is Pathogenic according to our data. Variant chr9-133524843-A-T is described in ClinVar as Pathogenic. ClinVar VariationId is 430842.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080483.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYMK	NM_001080483.3	MANE Select	c.2T>A	p.Met1?	start_lost	Exon 1 of 5	NP_001073952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYMK	ENST00000339996.4	TSL:2 MANE Select	c.2T>A	p.Met1?	start_lost	Exon 1 of 5	ENSP00000419712.2
	MYMK	ENST00000413714.1	TSL:3	n.190+3580T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Congenital nonprogressive myopathy with Moebius and Robin sequences (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.49	T
PhyloP100		6.1
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.92
MutPred		0.92		Loss of helix (P = 0.0041)
MVP		0.56
ClinPred		0.99	D
GERP RS		4.2
PromoterAI		0.0020	Neutral
Varity_R		0.84
gMVP		0.97
Mutation Taster		=14/186	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1131692248; hg19: chr9-136389965;