9-133514768-A-G

Variant names:

• chr9-133514768-A-G
• rs17758315
• NM_001080483.3:c.534T>C

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.534T>C​(p.Tyr178Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,613,678 control chromosomes in the GnomAD database, including 324,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30203 hom., cov: 33)
  • Exomes 𝑓: 0.63 (293879 hom.)
• Consequence: MYMK NM_001080483.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0680
• Publications: 16 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=-0.73).
• BP6: Variant 9-133514768-A-G is Benign according to our data. Variant chr9-133514768-A-G is described in ClinVar as Benign. ClinVar VariationId is 1179965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.734 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.534T>C	p.Tyr178Tyr	synonymous	Exon 5 of 5	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.534T>C	p.Tyr178Tyr	synonymous	Exon 5 of 5	ENSP00000419712.2	A6NI61

Frequencies

GnomAD3 genomes AF: 0.625 AC: 95029 AN: 152000 Hom.: 30182 Cov.: 33

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.674

GnomAD2 exomes AF: 0.620 AC: 155458 AN: 250684 AF XY: 0.611

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.781

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.664

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.614

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.631 AC: 921861 AN: 1461560 Hom.: 293879 Cov.: 57 AF XY: 0.626 AC XY: 455352 AN XY: 727090

African (AFR) AF: 0.634 AC: 21238 AN: 33474

American (AMR) AF: 0.779 AC: 34799 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 16241 AN: 26112

East Asian (EAS) AF: 0.652 AC: 25864 AN: 39698

South Asian (SAS) AF: 0.536 AC: 46248 AN: 86248

European-Finnish (FIN) AF: 0.462 AC: 24675 AN: 53404

Middle Eastern (MID) AF: 0.669 AC: 3859 AN: 5764

European-Non Finnish (NFE) AF: 0.639 AC: 710629 AN: 1111782

Other (OTH) AF: 0.634 AC: 38308 AN: 60378

GnomAD4 genome AF: 0.625 AC: 95097 AN: 152118 Hom.: 30203 Cov.: 33 AF XY: 0.621 AC XY: 46169 AN XY: 74348

African (AFR) AF: 0.635 AC: 26339 AN: 41510

American (AMR) AF: 0.746 AC: 11408 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3450 AN: 5150

South Asian (SAS) AF: 0.537 AC: 2588 AN: 4820

European-Finnish (FIN) AF: 0.449 AC: 4760 AN: 10604

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42217 AN: 67944

Other (OTH) AF: 0.671 AC: 1418 AN: 2114

Alfa AF: 0.623 Hom.: 30434

Bravo AF: 0.653

Asia WGS AF: 0.628 AC: 2184 AN: 3478

EpiCase AF: 0.636

EpiControl AF: 0.642

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital nonprogressive myopathy with Moebius and Robin sequences (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		-0.068
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: rs17758315; hg19: chr9-136379890; COSMIC: COSV60600221; COSMIC: COSV60600221;