Variant 10-119029854-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_199461.4(NANOS1):c.53C>T(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,231,014 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

NANOS1
NM_199461.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.0440

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008654565).

BP6

Variant 10-119029854-C-T is Benign according to our data. Variant chr10-119029854-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2350957.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS2

High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NANOS1	NM_199461.4 linkuse as main transcript	c.53C>T	p.Pro18Leu	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.53C>T	p.Pro18Leu	missense_variant	1/1	6	NM_199461.4	ENSP00000393275.1		Q8WY41

Frequencies

GnomAD3 genomes

AF:

0.000469

AC:

AN:

149304

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000894

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00176

AC:

AN:

2836

Hom.:

AF XY:

0.00224

AC XY:

AN XY:

1786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00355

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00128

AC:

1386

AN:

1081600

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

699

AN XY:

518570

show subpopulations

Gnomad4 AFR exome

AF:

0.0000907

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000920

Gnomad4 FIN exome

AF:

0.0000943

Gnomad4 NFE exome

AF:

0.00142

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000468

AC:

AN:

149414

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

AN XY:

72932

show subpopulations

Gnomad4 AFR

AF:

0.000219

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000894

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000106

Hom.:

Bravo

AF:

0.000559

ExAC

AF:

0.000345

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.53C>T (p.P18L) alteration is located in exon 1 (coding exon 1) of the NANOS1 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

NANOS1: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.1

REVEL

Benign

0.052

Sift

Uncertain

0.023

Sift4G

Benign

0.27

Polyphen

0.023

Vest4

0.13

MVP

0.56

ClinPred

0.057

GERP RS

2.9

Varity_R

0.081

gMVP

0.35

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