chr10-68210427-G-T

Position:

• chr10-68210427-G-T

Variant summary

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

The ENST00000358913.10(MYPN):​c.3935G>T​(p.Arg1312Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1312W) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYPN ENST00000358913.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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]

LOC124902443 (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=0.17216036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYPN	NM_032578.4	c.3935G>T	p.Arg1312Leu	missense_variant	20/20	ENST00000358913.10	NP_115967.2
LOC124902443	XR_007062176.1	n.127+4861C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10	c.3935G>T	p.Arg1312Leu	missense_variant	20/20	1	NM_032578.4	ENSP00000351790	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

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: 0.00

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	0.31
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	.;.;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T;.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.;N;.
MutationTaster	Benign	0.82	D;D;D
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.72	N;N;N;.
REVEL	Benign	0.033
Sift	Benign	0.091	T;T;T;.
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.32	B;B;B;.
Vest4		0.33
MutPred		0.24		Loss of catalytic residue at R1312 (P = 0.109);.;Loss of catalytic residue at R1312 (P = 0.109);.;
MVP		0.69
MPC		0.22
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.14
gMVP		0.24

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: rs761812034; hg19: chr10-69970184;