17-43753993-CT-C

Position:

• chr17-43753993-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025237.3(SOST):​c.*1348del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 148,718 control chromosomes in the GnomAD database, including 1,337 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (1337 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (0 hom.)
• Consequence: SOST NM_025237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83

Genes affected

SOST (HGNC:13771): (sclerostin) Sclerostin is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Loss-of-function mutations in this gene are associated with an autosomal-recessive disorder, sclerosteosis, which causes progressive bone overgrowth. A deletion downstream of this gene, which causes reduced sclerostin expression, is associated with a milder form of the disorder called van Buchem disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-43753993-CT-C is Benign according to our data. Variant chr17-43753993-CT-C is described in ClinVar as [Benign]. Clinvar id is 323429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOST	NM_025237.3	c.*1348del		3_prime_UTR_variant	2/2	ENST00000301691.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOST	ENST00000301691.3	c.*1348del		3_prime_UTR_variant	2/2	1	NM_025237.3	P1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 10911 AN: 148228 Hom.: 1318 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.00469

Gnomad EAS AF: 0.000783

Gnomad SAS AF: 0.00191

Gnomad FIN AF: 0.000628

Gnomad MID AF: 0.0162

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.0523

GnomAD4 exome AF: 0.00253 AC: 1 AN: 396 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242

Gnomad4 FIN exome AF: 0.00256

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0740 AC: 10975 AN: 148322 Hom.: 1337 Cov.: 31 AF XY: 0.0712 AC XY: 5145 AN XY: 72244

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.00469

Gnomad4 EAS AF: 0.000786

Gnomad4 SAS AF: 0.00192

Gnomad4 FIN AF: 0.000628

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.0518

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary bone dysplasia with increased bone density Benign:1

Benign, 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: rs563385804; hg19: chr17-41831361;