10-68145501-G-C

Variant names:

• chr10-68145501-G-C
• NM_032578.4:c.1105G>C

Variant summary

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

The NM_032578.4(MYPN):​c.1105G>C​(p.Asp369His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,200 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYPN NM_032578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4	c.1105G>C	p.Asp369His	missense_variant	Exon 4 of 20	ENST00000358913.10	NP_115967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10	c.1105G>C	p.Asp369His	missense_variant	Exon 4 of 20	1	NM_032578.4	ENSP00000351790.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461200 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726928

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	.;.;.;T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.74	T;T;.;T;T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.9	L;.;L;.;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N;N;N;.;N
REVEL	Benign	0.14
Sift	Uncertain	0.017	D;D;D;.;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		0.99	D;D;D;.;D
Vest4		0.42
MutPred		0.25		Gain of catalytic residue at D369 (P = 0.1374);.;Gain of catalytic residue at D369 (P = 0.1374);.;Gain of catalytic residue at D369 (P = 0.1374);
MVP		0.75
MPC		0.60
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-69905258;