rs8017377

Positions:

• chr14-24414681-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329

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]

ACMG classification

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	UniProt
NYNRIN	NM_025081.3	c.2932G>A	p.Ala978Thr	missense_variant	9/9	ENST00000382554.4
NYNRIN	XM_011537016.2	c.292G>A	p.Ala98Thr	missense_variant	4/4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52017 AN: 151932 Hom.: 10581 Cov.: 32

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

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.: 51 AF XY: 0.436 AC XY: 316871 AN XY: 726554

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.: 32 AF XY: 0.337 AC XY: 25036 AN XY: 74302

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.66
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.000092	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.63	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.0070
Sift	Benign	0.34	T
Sift4G	Benign	0.24	T
Polyphen		0.0020	B
Vest4		0.022
MPC		0.19
ClinPred		0.025	T
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

Other links and lift over

dbSNP: rs8017377; hg19: chr14-24883887; COSMIC: COSV66843153;