dbSNP rs3757302: OSTM1:c.783+27C>G (chr6-108051004-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014028.4(OSTM1):c.783+27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,557,642 control chromosomes in the GnomAD database, including 1,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.068 ( 680 hom., cov: 32)

Exomes 𝑓: 0.027 ( 955 hom. )

Consequence

OSTM1
NM_014028.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.595

Variant links:

Genes affected

OSTM1 (HGNC:21652): (osteoclastogenesis associated transmembrane protein 1) This gene encodes a protein that may be involved in the degradation of G proteins via the ubiquitin-dependent proteasome pathway. The encoded protein binds to members of subfamily A of the regulator of the G-protein signaling (RGS) family through an N-terminal leucine-rich region. This protein also has a central RING finger-like domain and E3 ubiquitin ligase activity. This protein is highly conserved from flies to humans. Defects in this gene may cause the autosomal recessive, infantile malignant form of osteopetrosis. [provided by RefSeq, Jul 2008]

OSTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-108051004-G-C is Benign according to our data. Variant chr6-108051004-G-C is described in ClinVar as [Benign]. Clinvar id is 1253226.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OSTM1	NM_014028.4 link	c.783+27C>G	intron_variant	Intron 4 of 5	ENST00000193322.8	NP_054747.2	Q86WC4
OSTM1	XM_047418679.1 link	c.783+27C>G	intron_variant	Intron 4 of 6		XP_047274635.1
OSTM1	XM_047418680.1 link	c.783+27C>G	intron_variant	Intron 4 of 5		XP_047274636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSTM1	ENST00000193322.8 link	c.783+27C>G		intron_variant	Intron 4 of 5	1	NM_014028.4	ENSP00000193322.3		Q86WC4

Frequencies

GnomAD3 genomes

AF:

0.0676

AC:

10282

AN:

151996

Hom.:

672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.0492

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0240

Gnomad OTH

AF:

0.0532

GnomAD3 exomes

AF:

0.0336

AC:

8427

AN:

250852

Hom.:

336

AF XY:

0.0294

AC XY:

3988

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.0353

Gnomad EAS exome

AF:

0.0491

Gnomad SAS exome

AF:

0.00389

Gnomad FIN exome

AF:

0.0279

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0271

AC:

38021

AN:

1405528

Hom.:

955

Cov.:

AF XY:

0.0259

AC XY:

18218

AN XY:

702586

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.0380

Gnomad4 SAS exome

AF:

0.00420

Gnomad4 FIN exome

AF:

0.0276

Gnomad4 NFE exome

AF:

0.0236

Gnomad4 OTH exome

AF:

0.0343

GnomAD4 genome

AF:

0.0678

AC:

10320

AN:

152114

Hom.:

680

Cov.:

AF XY:

0.0671

AC XY:

4989

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.0412

Gnomad4 ASJ

AF:

0.0374

Gnomad4 EAS

AF:

0.0490

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0301

Gnomad4 NFE

AF:

0.0240

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.0436

Hom.:

Bravo

AF:

0.0737

Asia WGS

AF:

0.0280

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.055

DANN

Benign

0.70

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