6-108042414-C-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014028.4(OSTM1):c.*2370_*2371insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.081 (791 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OSTM1 NM_014028.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.486

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSTM1	NM_014028.4	c.*2370_*2371insA		3_prime_UTR_variant	6/6	ENST00000193322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSTM1	ENST00000193322.8	c.*2370_*2371insA		3_prime_UTR_variant	6/6	1	NM_014028.4	P1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 10415 AN: 128796 Hom.: 790 Cov.: 0

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0420

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0606

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0809 AC: 10417 AN: 128828 Hom.: 791 Cov.: 0 AF XY: 0.0810 AC XY: 4991 AN XY: 61596

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.0420

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.0965

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0602

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Osteopetrosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs58798743; hg19: chr6-108363618;