Variant 10-119029901-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199461.4(NANOS1):c.100C>A(p.Pro34Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 1,386,522 control chromosomes in the GnomAD database, including 1,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.036 ( 145 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1678 hom. )

Consequence

NANOS1
NM_199461.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.977

Variant links:

Genes affected

NANOS1 (HGNC:23044): (nanos C2HC-type zinc finger 1) This gene encodes a CCHC-type zinc finger protein that is a member of the nanos family. This protein co-localizes with the RNA-binding protein pumilio RNA-binding family member 2 and may be involved in regulating translation as a post-transcriptional repressor. Mutations in this gene are associated with spermatogenic impairment. [provided by RefSeq, Sep 2015]

NANOS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022182167).

BP6

Variant 10-119029901-C-A is Benign according to our data. Variant chr10-119029901-C-A is described in ClinVar as [Benign]. Clinvar id is 1233504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NANOS1	NM_199461.4 linkuse as main transcript	c.100C>A	p.Pro34Thr	missense_variant	1/1	ENST00000425699.3	NP_955631.1	Q8WY41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NANOS1	ENST00000425699.3 linkuse as main transcript	c.100C>A	p.Pro34Thr	missense_variant	1/1	6	NM_199461.4	ENSP00000393275.1		Q8WY41

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

5468

AN:

150876

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00865

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.0308

Gnomad FIN

AF:

0.0765

Gnomad MID

AF:

0.0160

Gnomad NFE

AF:

0.0548

Gnomad OTH

AF:

0.0324

GnomAD3 exomes

AF:

0.0357

AC:

2394

AN:

67060

Hom.:

AF XY:

0.0366

AC XY:

1427

AN XY:

38980

show subpopulations

Gnomad AFR exome

AF:

0.00623

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0295

Gnomad FIN exome

AF:

0.0772

Gnomad NFE exome

AF:

0.0511

Gnomad OTH exome

AF:

0.0306

GnomAD4 exome

AF:

0.0489

AC:

60418

AN:

1235536

Hom.:

1678

Cov.:

AF XY:

0.0483

AC XY:

29321

AN XY:

607036

show subpopulations

Gnomad4 AFR exome

AF:

0.00573

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.0000373

Gnomad4 SAS exome

AF:

0.0293

Gnomad4 FIN exome

AF:

0.0760

Gnomad4 NFE exome

AF:

0.0536

Gnomad4 OTH exome

AF:

0.0393

GnomAD4 genome

AF:

0.0362

AC:

5467

AN:

150986

Hom.:

145

Cov.:

AF XY:

0.0368

AC XY:

2718

AN XY:

73782

show subpopulations

Gnomad4 AFR

AF:

0.00863

Gnomad4 AMR

AF:

0.0222

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.0306

Gnomad4 FIN

AF:

0.0765

Gnomad4 NFE

AF:

0.0548

Gnomad4 OTH

AF:

0.0320

Alfa

AF:

0.0467

Hom.:

Bravo

AF:

0.0302

ExAC

AF:

0.0135

AC:

498

Asia WGS

AF:

0.0130

AC:

AN:

3408

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	This variant is associated with the following publications: (PMID: 32155011) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.35

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.0

REVEL

Benign

0.056

Sift

Uncertain

0.010

Sift4G

Benign

0.12

Polyphen

0.59

Vest4

0.043

ClinPred

0.0071

GERP RS

3.6

Varity_R

0.13

gMVP

0.28

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