10-68174164-G-C

Variant names:

• chr10-68174164-G-C
• rs10997975
• NM_032578.4:c.2072G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032578.4(MYPN):​c.2072G>C​(p.Ser691Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S691N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYPN NM_032578.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.447

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04445234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4	c.2072G>C	p.Ser691Thr	missense_variant	Exon 11 of 20	ENST00000358913.10	NP_115967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10	c.2072G>C	p.Ser691Thr	missense_variant	Exon 11 of 20	1	NM_032578.4	ENSP00000351790.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

Apr 27, 2012

Leiden Muscular Dystrophy (MYPN)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.019	.;.;.;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.16	T;T;.;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.044	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.;N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.23	N;N;N;.
REVEL	Benign	0.015
Sift	Benign	0.040	D;D;D;.
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.11
MutPred		0.21		Loss of sheet (P = 0.0181);.;Loss of sheet (P = 0.0181);.;
MVP		0.41
MPC		0.13
ClinPred		0.090	T
GERP RS		3.2
Varity_R		0.060
gMVP		0.074

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

Publications

LitVar

Other links and lift over

dbSNP: rs10997975; hg19: chr10-69933921;