Genetic Variant NANOS1:p.Ala173dup (chr10-119030300-C-CCCG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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 -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 VariationId is 3049116.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 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 GnomAdExome4. There are 629 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 690 Unknown,AD 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOS1	NM_199461.4	MANE Select	c.517_519dupGCC	p.Ala173dup	conservative_inframe_insertion	Exon 1 of 1	NP_955631.1	Q8WY41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANOS1	ENST00000425699.3	TSL:6 MANE Select	c.517_519dupGCC	p.Ala173dup	conservative_inframe_insertion	Exon 1 of 1	ENSP00000393275.1	Q8WY41
	NANOS1	ENST00000340087.5	TSL:6	c.-126_-125insCCG		upstream_gene	N/A	ENSP00000345924.5	Q5T9H5

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

GnomAD2 exomes

AF:

0.00203

AC:

AN:

492

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ 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

African (AFR)

AF:

0.0127

AC:

254

AN:

20054

American (AMR)

AF:

0.00235

AC:

AN:

5958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11002

East Asian (EAS)

AF:

0.0170

AC:

323

AN:

18958

South Asian (SAS)

AF:

0.00227

AC:

AN:

18902

European-Finnish (FIN)

AF:

0.000173

AC:

AN:

17342

Middle Eastern (MID)

AF:

0.00119

AC:

AN:

2528

European-Non Finnish (NFE)

AF:

0.000806

AC:

704

AN:

873622

Other (OTH)

AF:

0.00155

AC:

AN:

38176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

164

247

329

411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00467

AC:

690

AN:

147636

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

325

AN XY:

71962

show subpopulations

African (AFR)

AF:

0.0125

AC:

511

AN:

41022

American (AMR)

AF:

0.00154

AC:

AN:

14902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.0170

AC:

AN:

5072

South Asian (SAS)

AF:

0.00228

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000449

AC:

AN:

8910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000739

AC:

AN:

66274

Other (OTH)

AF:

0.00293

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000109

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NANOS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCG

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

Computational scores

Splicing

Publications

Other links and lift over