Genetic Variant NANOS1:p.Ala171_Ala173dup (chr10-119030300-C-CCCGCCGCCG) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM4BS2_Supporting

The NM_199461.4(NANOS1):c.511_519dupGCCGCCGCC(p.Ala171_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 0.000026 in 1,154,096 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

NANOS1
NM_199461.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_199461.4.

BS2

High AC in GnomAd4 at 15 AD,Unknown gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.511_519dupGCCGCCGCC	p.Ala171_Ala173dup	conservative_inframe_insertion	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.511_519dupGCCGCCGCC	p.Ala171_Ala173dup	conservative_inframe_insertion	Exon 1 of 1	ENSP00000393275.1
	NANOS1	ENST00000340087.5	TSL:6	c.-126_-125insCCGCCGCCG		upstream_gene	N/A	ENSP00000345924.5

Frequencies

GnomAD3 genomes

AF:

0.000102

AC:

AN:

147538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000302

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

1006558

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

474868

show subpopulations

African (AFR)

AF:

0.000199

AC:

AN:

20058

American (AMR)

AF:

0.00

AC:

AN:

5958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11002

East Asian (EAS)

AF:

0.00

AC:

AN:

18964

South Asian (SAS)

AF:

0.00

AC:

AN:

18904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2528

European-Non Finnish (NFE)

AF:

0.0000103

AC:

AN:

873626

Other (OTH)

AF:

0.0000524

AC:

AN:

38176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000102

AC:

AN:

147538

Hom.:

Cov.:

AF XY:

0.0000974

AC XY:

AN XY:

71850

show subpopulations

African (AFR)

AF:

0.000318

AC:

AN:

40912

American (AMR)

AF:

0.00

AC:

AN:

14884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000302

AC:

AN:

66284

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

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-CCCGCCGCCGCCGCCGCCGCCG

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