16-58020561-C-CCT

Position:

• chr16-58020561-C-CCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024598.4(USB1):​c.*321_*322dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0074 (85 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: USB1 NM_024598.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

USB1 (HGNC:25792): (U6 snRNA biogenesis phosphodiesterase 1) This gene encodes a protein with several conserved domains, however, its exact function is not known. Mutations in this gene are associated with poikiloderma with neutropenia (PN), which shows phenotypic overlap with Rothmund-Thomson syndrome (RTS) caused by mutations in the RECQL4 gene. It is believed that this gene product interacts with RECQL4 protein via SMAD4 proteins, explaining the partial clinical overlap between PN and RTS. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00147 (337/228842) while in subpopulation AFR AF= 0.0348 (225/6460). AF 95% confidence interval is 0.0311. There are 11 homozygotes in gnomad4_exome. There are 162 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USB1	NM_024598.4	c.*321_*322dup		3_prime_UTR_variant	7/7	ENST00000219281.8	NP_078874.2
USB1	NM_001195302.2	c.*321_*322dup		3_prime_UTR_variant	6/6		NP_001182231.1
USB1	NM_001330568.2	c.*321_*322dup		3_prime_UTR_variant	7/7		NP_001317497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USB1	ENST00000219281.8	c.*321_*322dup		3_prime_UTR_variant	7/7	1	NM_024598.4	ENSP00000219281

Frequencies

GnomAD3 genomes AF: 0.00 AC: 905 AN: 122962 Hom.: 84 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.000307

Gnomad EAS AF: 0.000248

Gnomad SAS AF: 0.000294

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000260

Gnomad OTH AF: 0.00468

GnomAD4 exome AF: 0.00147 AC: 337 AN: 228842 Hom.: 11 Cov.: 0 AF XY: 0.00131 AC XY: 162 AN XY: 123944

Gnomad4 AFR exome AF: 0.0348

Gnomad4 AMR exome AF: 0.00245

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000455

Gnomad4 SAS exome AF: 0.000613

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00741 AC: 912 AN: 123094 Hom.: 85 Cov.: 0 AF XY: 0.00786 AC XY: 460 AN XY: 58546

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.000307

Gnomad4 EAS AF: 0.000248

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000260

Gnomad4 OTH AF: 0.00462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs58782258; hg19: chr16-58054465;