Variant 10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BS1BS2

The NM_199461.4(NANOS1):c.517_519dupGCC(p.Ala173dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,154,178 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

NANOS1
NM_199461.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.46

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 -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_199461.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 10-119030300-C-CCCG is Benign according to our data. Variant chr10-119030300-C-CCCG is described in ClinVar as [Benign]. Clinvar id is 3049116.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00139 (1403/1006542) while in subpopulation EAS AF= 0.017 (323/18958). AF 95% confidence interval is 0.0155. There are 3 homozygotes in gnomad4_exome. There are 629 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 690 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NANOS1	NM_199461.4 linkuse as main transcript	c.517_519dupGCC	p.Ala173dup	conservative_inframe_insertion	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.517_519dupGCC	p.Ala173dup	conservative_inframe_insertion	1/1	6	NM_199461.4	ENSP00000393275.1		Q8WY41

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

685

AN:

147534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00155

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0169

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000449

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000739

Gnomad OTH

AF:

0.00296

GnomAD3 exomes

AF:

0.00203

AC:

AN:

492

Hom.:

AF XY:

0.00

AC XY:

AN XY:

272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00139

AC:

1403

AN:

1006542

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

629

AN XY:

474864

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0170

Gnomad4 SAS exome

AF:

0.00227

Gnomad4 FIN exome

AF:

0.000173

Gnomad4 NFE exome

AF:

0.000806

Gnomad4 OTH exome

AF:

0.00155

GnomAD4 genome

AF:

0.00467

AC:

690

AN:

147636

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

325

AN XY:

71962

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.00154

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0170

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000449

Gnomad4 NFE

AF:

0.000739

Gnomad4 OTH

AF:

0.00293

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NANOS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 14, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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