Genetic Variant OSTM1:c.*2547G>A (chr6-108042238-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014028.4(OSTM1):c.*2547G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 122,590 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.048 ( 435 hom., cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OSTM1
NM_014028.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.130

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive osteopetrosis 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
infantile osteopetrosis with neuroaxonal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OSTM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-108042238-C-T is Benign according to our data. Variant chr6-108042238-C-T is described in ClinVar as Benign. ClinVar VariationId is 354934.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014028.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSTM1	NM_014028.4	MANE Select	c.*2547G>A		3_prime_UTR	Exon 6 of 6	NP_054747.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OSTM1	ENST00000193322.8	TSL:1 MANE Select	c.*2547G>A	3_prime_UTR	Exon 6 of 6	ENSP00000193322.3	Q86WC4
OSTM1	ENST00000492130.2	TSL:1	n.*2245G>A	non_coding_transcript_exon	Exon 7 of 7	ENSP00000514453.1	Q86WC4
OSTM1	ENST00000492130.2	TSL:1	n.*2245G>A	3_prime_UTR	Exon 7 of 7	ENSP00000514453.1	Q86WC4

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

5902

AN:

122560

Hom.:

434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.000599

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00581

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0391

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0481

AC:

5902

AN:

122590

Hom.:

435

Cov.:

AF XY:

0.0485

AC XY:

2736

AN XY:

56448

show subpopulations

African (AFR)

AF:

0.173

AC:

5618

AN:

32416

American (AMR)

AF:

0.0199

AC:

184

AN:

9232

Ashkenazi Jewish (ASJ)

AF:

0.000599

AC:

AN:

3338

East Asian (EAS)

AF:

0.00

AC:

AN:

4274

South Asian (SAS)

AF:

0.00

AC:

AN:

3936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4012

Middle Eastern (MID)

AF:

0.00610

AC:

AN:

164

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

62796

Other (OTH)

AF:

0.0387

AC:

AN:

1576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

231

462

693

924

1155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0482

Hom.:

Bravo

AF:

0.0505

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive osteopetrosis 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

(source)

DANN

Benign

0.25

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over