Genetic Variant NANOS1:p.Ala171_Ala173del (chr10-119030300-CCCGCCGCCG-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM4BP6BS2

The NM_199461.4(NANOS1):c.511_519delGCCGCCGCC(p.Ala171_Ala173del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 1,154,190 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 2 hom. )

Consequence

NANOS1
NM_199461.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely 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: Likely_benign. The variant received -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_199461.4.

BP6

Variant 10-119030300-CCCGCCGCCG-C is Benign according to our data. Variant chr10-119030300-CCCGCCGCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3042603.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 88 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.511_519delGCCGCCGCC	p.Ala171_Ala173del	conservative_inframe_deletion	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.511_519delGCCGCCGCC	p.Ala171_Ala173del	conservative_inframe_deletion	Exon 1 of 1	ENSP00000393275.1	Q8WY41
	NANOS1	ENST00000340087.5	TSL:6	c.-125_-117delCCGCCGCCG		upstream_gene	N/A	ENSP00000345924.5	Q5T9H5

Frequencies

GnomAD3 genomes

AF:

0.000596

AC:

AN:

147534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000202

Gnomad ASJ

AF:

0.00265

Gnomad EAS

AF:

0.000590

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.000679

Gnomad OTH

AF:

0.000986

GnomAD2 exomes

AF:

0.00

AC:

AN:

492

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000610

AC:

614

AN:

1006554

Hom.:

AF XY:

0.000630

AC XY:

299

AN XY:

474866

show subpopulations

African (AFR)

AF:

0.0000997

AC:

AN:

20058

American (AMR)

AF:

0.00134

AC:

AN:

5958

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

11002

East Asian (EAS)

AF:

0.000686

AC:

AN:

18964

South Asian (SAS)

AF:

0.0000529

AC:

AN:

18904

European-Finnish (FIN)

AF:

0.000519

AC:

AN:

17342

Middle Eastern (MID)

AF:

0.00396

AC:

AN:

2528

European-Non Finnish (NFE)

AF:

0.000603

AC:

527

AN:

873624

Other (OTH)

AF:

0.000733

AC:

AN:

38174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<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:

0.000596

AC:

AN:

147636

Hom.:

Cov.:

AF XY:

0.000695

AC XY:

AN XY:

71960

show subpopulations

African (AFR)

AF:

0.000317

AC:

AN:

41024

American (AMR)

AF:

0.000201

AC:

AN:

14902

Ashkenazi Jewish (ASJ)

AF:

0.00265

AC:

AN:

3396

East Asian (EAS)

AF:

0.000591

AC:

AN:

5072

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

8908

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000679

AC:

AN:

66274

Other (OTH)

AF:

0.000976

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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.:

Bravo

AF:

0.000589

ClinVar

ClinVar submissions

Significance:Likely 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

=174/26

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-CCCG

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