chr10-68121394-C-T

Variant summary

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

The NM_032578.4(MYPN):​c.-1-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,570,368 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 62 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 55 hom. )

Consequence

MYPN
NM_032578.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.116
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]

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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=-0.73).
BP6
Variant 10-68121394-C-T is Benign according to our data. Variant chr10-68121394-C-T is described in ClinVar as [Benign]. Clinvar id is 1268670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYPNNM_032578.4 linkuse as main transcriptc.-1-44C>T intron_variant ENST00000358913.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYPNENST00000358913.10 linkuse as main transcriptc.-1-44C>T intron_variant 1 NM_032578.4 P1Q86TC9-1

Frequencies

GnomAD3 genomes
AF:
0.0169
AC:
2570
AN:
152064
Hom.:
62
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0581
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00707
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00455
AC:
1057
AN:
232252
Hom.:
20
AF XY:
0.00349
AC XY:
439
AN XY:
125716
show subpopulations
Gnomad AFR exome
AF:
0.0584
Gnomad AMR exome
AF:
0.00377
Gnomad ASJ exome
AF:
0.000239
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000750
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000224
Gnomad OTH exome
AF:
0.00345
GnomAD4 exome
AF:
0.00179
AC:
2538
AN:
1418186
Hom.:
55
Cov.:
28
AF XY:
0.00160
AC XY:
1125
AN XY:
705162
show subpopulations
Gnomad4 AFR exome
AF:
0.0597
Gnomad4 AMR exome
AF:
0.00414
Gnomad4 ASJ exome
AF:
0.000204
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000856
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000188
Gnomad4 OTH exome
AF:
0.00409
GnomAD4 genome
AF:
0.0169
AC:
2576
AN:
152182
Hom.:
62
Cov.:
32
AF XY:
0.0170
AC XY:
1264
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0581
Gnomad4 AMR
AF:
0.00706
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.0141
Hom.:
9
Bravo
AF:
0.0202
Asia WGS
AF:
0.00346
AC:
12
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
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
7.4
DANN
Benign
0.74

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.

Other links and lift over

dbSNP: rs71578988; hg19: chr10-69881151; API