9-133518847-G-C

Variant names:

• chr9-133518847-G-C
• rs113493626
• NM_001080483.3:c.399+27C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080483.3(MYMK):​c.399+27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,592,988 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (71 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (62 hom.)
• Consequence: MYMK NM_001080483.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.278
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-133518847-G-C is Benign according to our data. Variant chr9-133518847-G-C is described in ClinVar as Benign. ClinVar VariationId is 1233419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0546 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+27C>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+27C>G		intron	N/A	ENSP00000419712.2	A6NI61
	MYMK	ENST00000413714.1	TSL:3	n.454+27C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2491 AN: 152056 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

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: 0.000382

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00459 AC: 1106 AN: 241024 AF XY: 0.00338

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000554

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000303

Gnomad OTH exome AF: 0.00187

GnomAD4 exome AF: 0.00176 AC: 2538 AN: 1440814 Hom.: 62 Cov.: 31 AF XY: 0.00154 AC XY: 1096 AN XY: 713584

African (AFR) AF: 0.0540 AC: 1786 AN: 33098

American (AMR) AF: 0.00420 AC: 184 AN: 43860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.00 AC: 0 AN: 39028

South Asian (SAS) AF: 0.0000587 AC: 5 AN: 85174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50198

Middle Eastern (MID) AF: 0.00283 AC: 16 AN: 5656

European-Non Finnish (NFE) AF: 0.000253 AC: 278 AN: 1098602

Other (OTH) AF: 0.00452 AC: 269 AN: 59464

GnomAD4 genome AF: 0.0164 AC: 2500 AN: 152174 Hom.: 71 Cov.: 32 AF XY: 0.0150 AC XY: 1119 AN XY: 74386

African (AFR) AF: 0.0565 AC: 2347 AN: 41508

American (AMR) AF: 0.00680 AC: 104 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 67996

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00264 Hom.: 1

Bravo AF: 0.0192

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.66
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs113493626; hg19: chr9-136383969;