chr9-133514993-A-C

Variant names:

• chr9-133514993-A-C
• rs9802285
• NM_001080483.3:c.517-208T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080483.3(MYMK):​c.517-208T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 150,848 control chromosomes in the GnomAD database, including 10,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10338 hom., cov: 32)
• Consequence: MYMK NM_001080483.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.29
• Publications: 2 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: ClinGen, Illumina, Genomics England PanelApp, Orphanet
• Carey-Fineman-Ziter syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-133514993-A-C is Benign according to our data. Variant chr9-133514993-A-C is described in ClinVar as Benign. ClinVar VariationId is 1225528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYMK	NM_001080483.3	MANE Select	c.517-208T>G		intron	N/A	NP_001073952.1	A6NI61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYMK	ENST00000339996.4	TSL:2 MANE Select	c.517-208T>G		intron	N/A	ENSP00000419712.2	A6NI61

Frequencies

GnomAD3 genomes AF: 0.357 AC: 53814 AN: 150730 Hom.: 10329 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.357 AC: 53851 AN: 150848 Hom.: 10338 Cov.: 32 AF XY: 0.359 AC XY: 26409 AN XY: 73612

African (AFR) AF: 0.299 AC: 12243 AN: 41014

American (AMR) AF: 0.509 AC: 7748 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1575 AN: 3456

East Asian (EAS) AF: 0.635 AC: 3252 AN: 5122

South Asian (SAS) AF: 0.468 AC: 2230 AN: 4768

European-Finnish (FIN) AF: 0.220 AC: 2286 AN: 10378

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23298 AN: 67590

Other (OTH) AF: 0.390 AC: 819 AN: 2102

Alfa AF: 0.326 Hom.: 1044

Bravo AF: 0.376

Asia WGS AF: 0.507 AC: 1759 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.66
DANN	Benign	0.77
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs9802285; hg19: chr9-136380115; COSMIC: COSV60600787; COSMIC: COSV60600787;