rs199476407

Variant names:

• chr10-68158587-T-C
• rs199476407
• NM_032578.4:c.1419T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS1

The NM_032578.4(MYPN):​c.1419T>C​(p.Thr473Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,450,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: MYPN NM_032578.4 synonymous
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.412
• Publications: 0 publications found

Genes affected

MYPN (HGNC:23246): (myopalladin) Striated muscle in vertebrates comprises large proteins which must be organized properly to contract efficiently. Z-lines in striated muscle are a sign of this organization, representing the ends of actin thin filaments, titin, nebulin or nebulette and accessory proteins required for structure and function. This gene encodes a protein which interacts with nebulin in skeletal muscle or nebulette in cardiac muscle and alpha-actinin. In addition, this gene product can interact with a protein with the I-band indicating it has a regulatory as well as structural function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

RN7SKP202 (HGNC:45926): (RN7SK pseudogene 202)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.412 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000827 (12/1450604) while in subpopulation EAS AF = 0.000278 (11/39602). AF 95% confidence interval is 0.000155. There are 0 homozygotes in GnomAdExome4. There are 5 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032578.4. 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
	MYPN	NM_032578.4	MANE Select	c.1419T>C	p.Thr473Thr	synonymous	Exon 7 of 20	NP_115967.2	Q86TC9-1
	MYPN	NM_001256267.2		c.1419T>C	p.Thr473Thr	synonymous	Exon 8 of 21	NP_001243196.1	Q86TC9-1
	MYPN	NM_001256268.2		c.537T>C	p.Thr179Thr	synonymous	Exon 11 of 24	NP_001243197.1	A0A087WX60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYPN	ENST00000358913.10	TSL:1 MANE Select	c.1419T>C	p.Thr473Thr	synonymous	Exon 7 of 20	ENSP00000351790.5	Q86TC9-1
	MYPN	ENST00000540630.6	TSL:1	c.1473T>C	p.Thr491Thr	synonymous	Exon 7 of 20	ENSP00000441668.3	A0A8J9ASZ5
	MYPN	ENST00000613327.5	TSL:1	c.1419T>C	p.Thr473Thr	synonymous	Exon 8 of 21	ENSP00000480757.2	Q86TC9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251040 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000827 AC: 12 AN: 1450604 Hom.: 0 Cov.: 29 AF XY: 0.00000692 AC XY: 5 AN XY: 722316

African (AFR) AF: 0.00 AC: 0 AN: 33160

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.000278 AC: 11 AN: 39602

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102054

Other (OTH) AF: 0.00 AC: 0 AN: 60026

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.41

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: rs199476407; hg19: chr10-69918344;