rs138678049

Variant names:

• chr5-137883389-T-C
• rs138678049
• NM_006790.3:c.822T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-137883389-T-C
• chr5-137883389-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006790.3(MYOT):​c.822T>C​(p.Ser274Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,613,996 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (3 hom.)
• Consequence: MYOT NM_006790.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.759
• Publications: 0 publications found

Genes affected

MYOT (HGNC:12399): (myotilin) This gene encodes a cystoskeletal protein which plays a significant role in the stability of thin filaments during muscle contraction. This protein binds F-actin, crosslinks actin filaments, and prevents latrunculin A-induced filament disassembly. Mutations in this gene have been associated with limb-girdle muscular dystrophy and myofibrillar myopathies. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.[provided by RefSeq, Oct 2008]

PKD2L2-DT (HGNC:55557): (PKD2L2 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-137883389-T-C is Benign according to our data. Variant chr5-137883389-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.759 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00182 (277/152316) while in subpopulation AFR AF = 0.0065 (270/41568). AF 95% confidence interval is 0.00586. There are 1 homozygotes in GnomAd4. There are 116 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 277 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006790.3. 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
	MYOT	NM_006790.3	MANE Select	c.822T>C	p.Ser274Ser	synonymous	Exon 7 of 10	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.477T>C	p.Ser159Ser	synonymous	Exon 8 of 11	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.270T>C	p.Ser90Ser	synonymous	Exon 7 of 10	NP_001129412.1	Q9UBF9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOT	ENST00000239926.9	TSL:1 MANE Select	c.822T>C	p.Ser274Ser	synonymous	Exon 7 of 10	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.819T>C	p.Ser273Ser	synonymous	Exon 7 of 10	ENSP00000638701.1
	MYOT	ENST00000968644.1		c.684T>C	p.Ser228Ser	synonymous	Exon 5 of 8	ENSP00000638703.1

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152198 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000474 AC: 119 AN: 251148 AF XY: 0.000354

Gnomad AFR exome AF: 0.00702

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000183 AC: 268 AN: 1461680 Hom.: 3 Cov.: 31 AF XY: 0.000158 AC XY: 115 AN XY: 727128

African (AFR) AF: 0.00726 AC: 243 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5750

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111898

Other (OTH) AF: 0.000232 AC: 14 AN: 60386

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152316 Hom.: 1 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74498

African (AFR) AF: 0.00650 AC: 270 AN: 41568

American (AMR) AF: 0.000262 AC: 4 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000703 Hom.: 1

Bravo AF: 0.00190

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Myofibrillar myopathy 3 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.76
Mutation Taster		=97/3	polymorphism

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: rs138678049; hg19: chr5-137219078;