16-57207890-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_133368.3(RSPRY1):c.351-167dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,242 control chromosomes in the GnomAD database, including 101 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.035 (101 hom., cov: 31)
• Consequence: RSPRY1 NM_133368.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.753

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 -10 ACMG points.

• BP6: Variant 16-57207890-A-AC is Benign according to our data. Variant chr16-57207890-A-AC is described in ClinVar as [Benign]. Clinvar id is 1259854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.035 (5328/152242) while in subpopulation NFE AF= 0.0378 (2568/68002). AF 95% confidence interval is 0.0365. There are 101 homozygotes in gnomad4. There are 2694 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPRY1	NM_133368.3	c.351-167dup		intron_variant		ENST00000394420.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPRY1	ENST00000394420.9	c.351-167dup		intron_variant		1	NM_133368.3	P1

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5330 AN: 152124 Hom.: 100 Cov.: 31

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0350 AC: 5328 AN: 152242 Hom.: 101 Cov.: 31 AF XY: 0.0362 AC XY: 2694 AN XY: 74460

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.0378

Gnomad4 OTH AF: 0.0573

Alfa AF: 0.0363 Hom.: 13

Bravo AF: 0.0332

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

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: rs201524384; hg19: chr16-57241802;