16-57205068-G-A

Position:

• chr16-57205068-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001305182.2(RSPRY1):​c.*56G>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 0.0379 in 1,264,694 control chromosomes in the GnomAD database, including 1,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (112 hom., cov: 32)
  • Exomes 𝑓: 0.038 (954 hom.)
• Consequence: RSPRY1 NM_001305182.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.194

Genes affected

RSPRY1 (HGNC:29420): (ring finger and SPRY domain containing 1) This gene encodes a glycoprotein that contains a RING-type zinc finger domain and an SPRY domain of unknown function. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 16-57205068-G-A is Benign according to our data. Variant chr16-57205068-G-A is described in ClinVar as [Benign]. Clinvar id is 1283466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPRY1	NM_133368.3	c.350+60G>A		intron_variant		ENST00000394420.9	NP_588609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPRY1	ENST00000394420.9	c.350+60G>A		intron_variant		1	NM_133368.3	ENSP00000377942.4

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5698 AN: 152168 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0573

GnomAD4 exome AF: 0.0379 AC: 42214 AN: 1112408 Hom.: 954 Cov.: 15 AF XY: 0.0376 AC XY: 20846 AN XY: 554884

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.0000855

Gnomad4 SAS exome AF: 0.0180

Gnomad4 FIN exome AF: 0.0481

Gnomad4 NFE exome AF: 0.0390

Gnomad4 OTH exome AF: 0.0406

GnomAD4 genome AF: 0.0374 AC: 5700 AN: 152286 Hom.: 112 Cov.: 32 AF XY: 0.0384 AC XY: 2859 AN XY: 74466

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.0378

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0385 Hom.: 16

Bravo AF: 0.0362

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.4
DANN	Benign	0.77

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: rs112725750; hg19: chr16-57238980;