6-108041898-C-T

Position:

• chr6-108041898-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014028.4(OSTM1):​c.*2887G>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 0.0431 in 152,122 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (278 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: OSTM1 NM_014028.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.851

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-108041898-C-T is Benign according to our data. Variant chr6-108041898-C-T is described in ClinVar as [Benign]. Clinvar id is 354930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSTM1	NM_014028.4	c.*2887G>A		3_prime_UTR_variant	6/6	ENST00000193322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSTM1	ENST00000193322.8	c.*2887G>A		3_prime_UTR_variant	6/6	1	NM_014028.4	P1

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6545 AN: 152004 Hom.: 280 Cov.: 31

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0431 AC: 6553 AN: 152122 Hom.: 278 Cov.: 31 AF XY: 0.0461 AC XY: 3431 AN XY: 74354

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.0978

Gnomad4 FIN AF: 0.0584

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0211 Hom.: 18

Bravo AF: 0.0401

Asia WGS AF: 0.163 AC: 563 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive osteopetrosis 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.34

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: rs41287526; hg19: chr6-108363102;