NM_199461.4:c.240_242delCTC

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_199461.4(NANOS1):c.240_242delCTC(p.Ser81del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,385,068 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 35 hom. )

Consequence

NANOS1
NM_199461.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 2.57

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 12
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NANOS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant 10-119030030-CCCT-C is Benign according to our data. Variant chr10-119030030-CCCT-C is described in ClinVar as Benign. ClinVar VariationId is 65390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 865 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199461.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOS1	NM_199461.4	MANE Select	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 1	NP_955631.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOS1	ENST00000425699.3	TSL:6 MANE Select	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000393275.1

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

865

AN:

149962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00136

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.00526

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0337

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00642

Gnomad OTH

AF:

0.00194

GnomAD2 exomes

AF:

0.00376

AC:

147

AN:

39138

AF XY:

0.00391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000967

Gnomad ASJ exome

AF:

0.00252

Gnomad EAS exome

AF:

0.000745

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.00526

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00603

AC:

7446

AN:

1234998

Hom.:

AF XY:

0.00584

AC XY:

3529

AN XY:

604126

show subpopulations

African (AFR)

AF:

0.000671

AC:

AN:

25350

American (AMR)

AF:

0.000683

AC:

AN:

19024

Ashkenazi Jewish (ASJ)

AF:

0.00382

AC:

AN:

19884

East Asian (EAS)

AF:

0.0000369

AC:

AN:

27088

South Asian (SAS)

AF:

0.00146

AC:

AN:

58302

European-Finnish (FIN)

AF:

0.0257

AC:

766

AN:

29822

Middle Eastern (MID)

AF:

0.000266

AC:

AN:

3762

European-Non Finnish (NFE)

AF:

0.00623

AC:

6243

AN:

1001540

Other (OTH)

AF:

0.00486

AC:

244

AN:

50226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

386

771

1157

1542

1928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00576

AC:

865

AN:

150070

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

511

AN XY:

73236

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41360

American (AMR)

AF:

0.00105

AC:

AN:

15168

Ashkenazi Jewish (ASJ)

AF:

0.00526

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0337

AC:

335

AN:

9936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00642

AC:

430

AN:

66984

Other (OTH)

AF:

0.00192

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00245

Hom.:

Bravo

AF:

0.00311

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spermatogenic failure 12

Pathogenic:1Benign:1

Mar 01, 2013

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:curation

NM_199461.2:c.240_242delCTC in the NANOS1 gene has an allele frequency of 0.022 in European (Finnish) subpopulation in the gnomAD database. This in-frame deletion happens in a repetitive region without known function. Kusz-Zamelczyk et al. reported this variant as p.Pro77_Ser78delinsPro (PMID: 23315541). Using the quantitative yeast two-hybrid assay, the author tested both mutated NANOS1 alleles for interaction with GEMIN3, and found that the p.Pro34Thr, p.Pro77_Ser78delinsPro allele reduced interaction with GEMIN3 by 14% (PMID: 23315541). In one pedigree, the variant segregate with the phenotype. In contrary, in the second pedigree (patient 2), the father passed this variant to his son, indicating his father is fertile although he has this variant. Taken together, we interprete this variant as Benign/Likely benign variant (PMID: 23315541). ACMG/AMP criteria applied: BS1, BP3.

not provided

Benign:2

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NANOS1: PM4:Supporting, BS1, BS2

Jan 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NANOS1-related disorder

Benign:1

Mar 16, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=75/25

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over