rs6480314

chr10-68207690-G-Achr10-68207690-G-Cchr10-68207690-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032578.4(MYPN):c.3793+787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,180 control chromosomes in the GnomAD database, including 53,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53491 hom., cov: 33)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYPN	NM_032578.4	c.3793+787G>A		intron_variant		ENST00000358913.10
LOC124902443	XR_007062176.1	n.128-3431C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYPN	ENST00000358913.10	c.3793+787G>A		intron_variant		1	NM_032578.4	P1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127192 AN: 152060 Hom.: 53447 Cov.: 33

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.835

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.836 AC: 127288 AN: 152180 Hom.: 53491 Cov.: 33 AF XY: 0.834 AC XY: 62015 AN XY: 74376

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.837

Alfa AF: 0.823 Hom.: 76907

Bravo AF: 0.837

Asia WGS AF: 0.839 AC: 2917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.44
Dann	Benign	0.53

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: rs6480314; hg19: chr10-69967447;