Genetic Variant OBSCN:p.Ser7Arg (chr1-228211804-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001386125.1(OBSCN):c.21C>A(p.Ser7Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OBSCN
NM_001386125.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.74

Publications

0 publications found

Variant links:

Genes affected

OBSCN (HGNC:15719): (obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF) The obscurin gene spans more than 150 kb, contains over 80 exons and encodes a protein of approximately 720 kDa. The encoded protein contains 68 Ig domains, 2 fibronectin domains, 1 calcium/calmodulin-binding domain, 1 RhoGEF domain with an associated PH domain, and 2 serine-threonine kinase domains. This protein belongs to the family of giant sacromeric signaling proteins that includes titin and nebulin, and may have a role in the organization of myofibrils during assembly and may mediate interactions between the sarcoplasmic reticulum and myofibrils. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OBSCN links:

OBSCN-AS1 (HGNC:32047): (OBSCN antisense RNA 1)

OBSCN-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13596565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386125.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OBSCN	NM_001386125.1	MANE Select	c.21C>A	p.Ser7Arg	missense	Exon 2 of 116	NP_001373054.1	Q5VST9-7
OBSCN	NM_001271223.3		c.21C>A	p.Ser7Arg	missense	Exon 2 of 116	NP_001258152.2
OBSCN	NM_001098623.2		c.21C>A	p.Ser7Arg	missense	Exon 2 of 105	NP_001092093.2	A0ABB0I190

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OBSCN	ENST00000680850.1	MANE Select	c.21C>A	p.Ser7Arg	missense	Exon 2 of 116	ENSP00000505517.1	Q5VST9-7
OBSCN	ENST00000636476.2	TSL:1	c.21C>A	p.Ser7Arg	missense	Exon 1 of 104	ENSP00000489816.2	A0ABB0L580
OBSCN-AS1	ENST00000295012.5	TSL:1	n.239+1618G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1396698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686676

African (AFR)

AF:

0.00

AC:

AN:

31960

American (AMR)

AF:

0.00

AC:

AN:

38252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22100

East Asian (EAS)

AF:

0.00

AC:

AN:

38756

South Asian (SAS)

AF:

0.00

AC:

AN:

76240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4468

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078354

Other (OTH)

AF:

0.00

AC:

AN:

57332

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.047

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.074

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.9

PhyloP100

-1.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

REVEL

Benign

0.25

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.14

MutPred

0.30

Gain of MoRF binding (P = 0.0097)

MVP

0.42

MPC

2.2

ClinPred

0.88

GERP RS

-4.9

PromoterAI

-0.0052

Neutral

(source)

Varity_R

0.32

gMVP

0.56

Mutation Taster

=286/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over