Genetic Variant NM_032578.4:c.1318-318T>C (chr10-68158168-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032578.4(MYPN):c.1318-318T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 278,768 control chromosomes in the GnomAD database, including 81,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45583 hom., cov: 30)

Exomes 𝑓: 0.74 ( 35954 hom. )

Consequence

MYPN
NM_032578.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.14

Variant links:

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]

MYPN links:

RN7SKP202 (HGNC:45926): (RN7SK pseudogene 202)

RN7SKP202 links:

LOC107984240 (HGNC:):

LOC107984240 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 10-68158168-T-C is Benign according to our data. Variant chr10-68158168-T-C is described in ClinVar as [Benign]. Clinvar id is 683655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4 link	c.1318-318T>C		intron_variant	Intron 6 of 19	ENST00000358913.10	NP_115967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10 link	c.1318-318T>C		intron_variant	Intron 6 of 19	1	NM_032578.4	ENSP00000351790.5		Q86TC9-1

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

116328

AN:

151338

Hom.:

45530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.862

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.741

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.803

Gnomad MID

AF:

0.618

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.746

GnomAD4 exome

AF:

0.741

AC:

94333

AN:

127314

Hom.:

35954

Cov.:

AF XY:

0.736

AC XY:

49073

AN XY:

66694

show subpopulations

Gnomad4 AFR exome

AF:

0.874

Gnomad4 AMR exome

AF:

0.737

Gnomad4 ASJ exome

AF:

0.756

Gnomad4 EAS exome

AF:

0.332

Gnomad4 SAS exome

AF:

0.695

Gnomad4 FIN exome

AF:

0.794

Gnomad4 NFE exome

AF:

0.777

Gnomad4 OTH exome

AF:

0.748

GnomAD4 genome

AF:

0.769

AC:

116437

AN:

151454

Hom.:

45583

Cov.:

AF XY:

0.765

AC XY:

56570

AN XY:

73976

show subpopulations

Gnomad4 AFR

AF:

0.862

Gnomad4 AMR

AF:

0.741

Gnomad4 ASJ

AF:

0.748

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.647

Gnomad4 FIN

AF:

0.803

Gnomad4 NFE

AF:

0.758

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.792

Hom.:

6847

Bravo

AF:

0.768

Asia WGS

AF:

0.497

AC:

1729

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.6

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over