rs201225230

Positions:

• chr10-68148460-T-C
• chr10-68148460-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032578.4(MYPN):​c.1238T>C​(p.Ile413Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYPN NM_032578.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

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]

LOC107984240 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14559728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYPN	NM_032578.4	c.1238T>C	p.Ile413Thr	missense_variant	5/20	ENST00000358913.10	NP_115967.2
LOC107984240	XR_001747479.2	n.206-1742A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10	c.1238T>C	p.Ile413Thr	missense_variant	5/20	1	NM_032578.4	ENSP00000351790	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	.;.;.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.65	T;T;.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L;.;L;.;L
MutationTaster	Benign	0.58	D;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.70	N;N;N;.;N
REVEL	Benign	0.072
Sift	Benign	0.14	T;T;T;.;T
Sift4G	Benign	0.43	T;T;T;T;T
Polyphen		0.0020	B;B;B;.;B
Vest4		0.17
MutPred		0.45		Gain of disorder (P = 0.0146);.;Gain of disorder (P = 0.0146);.;Gain of disorder (P = 0.0146);
MVP		0.56
MPC		0.17
ClinPred		0.15	T
GERP RS		5.8
Varity_R		0.14
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201225230; hg19: chr10-69908217;