1-228307089-G-C

Variant names:

• chr1-228307089-G-C
• NM_001386125.1:c.14986G>C

Variant summary

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

The NM_001386125.1(OBSCN):​c.14986G>C​(p.Gly4996Arg) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OBSCN NM_001386125.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

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]

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=0.12907553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OBSCN	NM_001386125.1	c.14986G>C	p.Gly4996Arg	missense_variant	Exon 56 of 116	ENST00000680850.1	NP_001373054.1
OBSCN	NM_001271223.3	c.14986G>C	p.Gly4996Arg	missense_variant	Exon 56 of 116		NP_001258152.2
OBSCN	NM_001098623.2	c.12115G>C	p.Gly4039Arg	missense_variant	Exon 45 of 105		NP_001092093.2
OBSCN	NM_052843.4	c.12115G>C	p.Gly4039Arg	missense_variant	Exon 45 of 81		NP_443075.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBSCN	ENST00000680850.1	c.14986G>C	p.Gly4996Arg	missense_variant	Exon 56 of 116		NM_001386125.1	ENSP00000505517.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.2
DANN	Benign	0.67
DEOGEN2	Benign	0.095	.;T;.;.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.56	T;T;T;.;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L;L;.;.;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N;N;.;.;.
REVEL	Benign	0.028
Sift	Benign	0.46	T;T;.;.;.
Sift4G	Benign	0.21	T;T;D;D;.
Polyphen		0.027	B;P;.;.;P
Vest4		0.18
MutPred		0.45		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;.;Loss of sheet (P = 0.0315);
MVP		0.43
MPC		0.50
ClinPred		0.25	T
GERP RS		0.34
Varity_R		0.049
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-228494790;