chr9-133518513-T-C

Variant names:

• chr9-133518513-T-C
• rs62576043
• NM_001080483.3:c.399+361A>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.399+361A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,240 control chromosomes in the GnomAD database, including 5,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5220 hom., cov: 33)
• Consequence: MYMK NM_001080483.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.719
• Publications: 0 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 9-133518513-T-C is Benign according to our data. Variant chr9-133518513-T-C is described in ClinVar as Benign. ClinVar VariationId is 1269016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 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.399+361A>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.399+361A>G		intron	N/A	ENSP00000419712.2	A6NI61
	MYMK	ENST00000413714.1	TSL:3	n.454+361A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38397 AN: 152122 Hom.: 5224 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.252 AC: 38416 AN: 152240 Hom.: 5220 Cov.: 33 AF XY: 0.246 AC XY: 18293 AN XY: 74440

African (AFR) AF: 0.253 AC: 10527 AN: 41546

American (AMR) AF: 0.237 AC: 3618 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3470

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5182

South Asian (SAS) AF: 0.0652 AC: 315 AN: 4828

European-Finnish (FIN) AF: 0.227 AC: 2406 AN: 10602

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19689 AN: 68004

Other (OTH) AF: 0.273 AC: 576 AN: 2110

Alfa AF: 0.275 Hom.: 1186

Bravo AF: 0.258

Asia WGS AF: 0.0890 AC: 310 AN: 3478

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	0.30
DANN	Benign	0.57
PhyloP100		-0.72
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: rs62576043; hg19: chr9-136383635; COSMIC: COSV60600324;