Variant rs8017377 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_025081.3(NYNRIN):c.2932G>A(p.Ala978Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,612,694 control chromosomes in the GnomAD database, including 156,619 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 10575 hom., cov: 32)

Exomes 𝑓: 0.44 ( 146044 hom. )

Consequence

NYNRIN
NM_025081.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.329

Variant links:

Genes affected

NYNRIN (HGNC:20165): (NYN domain and retroviral integrase containing) Predicted to enable endoribonuclease activity and mRNA binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, endonucleolytic. Predicted to be integral component of membrane. Predicted to be active in cytoplasmic ribonucleoprotein granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NYNRIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.2463175E-5).

BP6

Variant 14-24414681-G-A is Benign according to our data. Variant chr14-24414681-G-A is described in ClinVar as [Benign]. Clinvar id is 2792733.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-24414681-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NYNRIN	NM_025081.3 linkuse as main transcript	c.2932G>A	p.Ala978Thr	missense_variant	9/9	ENST00000382554.4	NP_079357.2
NYNRIN	XM_011537016.2 linkuse as main transcript	c.292G>A	p.Ala98Thr	missense_variant	4/4		XP_011535318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NYNRIN	ENST00000382554.4 linkuse as main transcript	c.2932G>A	p.Ala978Thr	missense_variant	9/9	5	NM_025081.3	ENSP00000371994	P1	Q9P2P1-1
NYNRIN	ENST00000554505.1 linkuse as main transcript	n.388G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

52017

AN:

151932

Hom.:

10581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.476

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.0533

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.348

GnomAD3 exomes

AF:

0.366

AC:

90726

AN:

247982

Hom.:

19143

AF XY:

0.380

AC XY:

51029

AN XY:

134328

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.474

Gnomad EAS exome

AF:

0.0485

Gnomad SAS exome

AF:

0.377

Gnomad FIN exome

AF:

0.381

Gnomad NFE exome

AF:

0.477

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.436

AC:

636622

AN:

1460644

Hom.:

146044

Cov.:

AF XY:

0.436

AC XY:

316871

AN XY:

726554

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.0473

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.342

AC:

52019

AN:

152050

Hom.:

10575

Cov.:

AF XY:

0.337

AC XY:

25036

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.475

Gnomad4 EAS

AF:

0.0532

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.441

Hom.:

40216

Bravo

AF:

0.325

ESP6500AA

AF:

0.157

AC:

691

ESP6500EA

AF:

0.465

AC:

3981

ExAC

AF:

0.372

AC:

45108

Asia WGS

AF:

0.178

AC:

618

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.15

DANN

Benign

0.66

DEOGEN2

Benign

0.013

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.43

MetaRNN

Benign

0.000092

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.63

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.52

REVEL

Benign

0.0070

Sift

Benign

0.34

Sift4G

Benign

0.24

Polyphen

0.0020

Vest4

0.022

MPC

0.19

ClinPred

0.025

GERP RS

-9.1

Varity_R

0.016

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over