Variant chr10-119030036-T-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.235T>A(p.Ser79Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00914 in 1,374,902 control chromosomes in the GnomAD database, including 859 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 (★★).

Frequency

Genomes: 𝑓 0.046 ( 515 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 344 hom. )

Consequence

NANOS1
NM_199461.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.515

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=0.0012706518).

BP6

Variant 10-119030036-T-A is Benign according to our data. Variant chr10-119030036-T-A is described in ClinVar as [Benign]. Clinvar id is 768395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 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.235T>A	p.Ser79Thr	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.235T>A	p.Ser79Thr	missense_variant	1/1	6	NM_199461.4	ENSP00000393275.1		Q8WY41

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6851

AN:

149524

Hom.:

512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.000876

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000987

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.00531

AC:

181

AN:

34092

Hom.:

AF XY:

0.00337

AC XY:

AN XY:

19560

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.00915

Gnomad ASJ exome

AF:

0.000978

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000145

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000682

Gnomad OTH exome

AF:

0.00462

GnomAD4 exome

AF:

0.00465

AC:

5693

AN:

1225272

Hom.:

344

Cov.:

AF XY:

0.00413

AC XY:

2475

AN XY:

598574

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.00151

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000213

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000713

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0459

AC:

6868

AN:

149630

Hom.:

515

Cov.:

AF XY:

0.0442

AC XY:

3231

AN XY:

73034

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0198

Gnomad4 ASJ

AF:

0.000876

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000833

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000987

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.0235

Hom.:

Bravo

AF:

0.0526

ESP6500AA

AF:

0.0775

AC:

155

ESP6500EA

AF:

0.000704

AC:

ExAC

AF:

0.00119

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.37

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.24

REVEL

Benign

0.030

Sift

Benign

0.69

Sift4G

Benign

0.38

Polyphen

0.010

Vest4

0.16

MVP

0.27

ClinPred

0.0032

GERP RS

1.2

Varity_R

0.062

gMVP

0.11

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