rs538539239

Variant names:

• chr10-119030300-CCCGCCGCCGCCG-C
• rs538539239
• NM_199461.4:c.508_519delGCCGCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr10-119030300-CCCGCCGCCGCCG-C
• chr10-119030300-CCCGCCGCCGCCG-CCCG
• chr10-119030300-CCCGCCGCCGCCG-CCCGCCG
• chr10-119030300-CCCGCCGCCGCCG-CCCGCCGCCG
• chr10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCG
• chr10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCG
• chr10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCG
• chr10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCG
• chr10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM4 BS2_Supporting

The NM_199461.4(NANOS1):​c.508_519delGCCGCCGCCGCC​(p.Ala170_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 0.0000104 in 1,154,096 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: NANOS1 NM_199461.4 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 1 publications found

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)

ACMG classification

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 GnomAdExome4 at 10 AD,Unknown gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOS1	NM_199461.4	c.508_519delGCCGCCGCCGCC	p.Ala170_Ala173del	conservative_inframe_deletion	Exon 1 of 1	ENST00000425699.3	NP_955631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANOS1	ENST00000425699.3	c.508_519delGCCGCCGCCGCC	p.Ala170_Ala173del	conservative_inframe_deletion	Exon 1 of 1	6	NM_199461.4	ENSP00000393275.1
NANOS1	ENST00000340087.5	c.-125_-114delCCGCCGCCGCCG		upstream_gene_variant		6		ENSP00000345924.5

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147538 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

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: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000993 AC: 10 AN: 1006558 Hom.: 0 AF XY: 0.00000842 AC XY: 4 AN XY: 474868

African (AFR) AF: 0.0000499 AC: 1 AN: 20058

American (AMR) AF: 0.00 AC: 0 AN: 5958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11002

East Asian (EAS) AF: 0.00 AC: 0 AN: 18964

South Asian (SAS) AF: 0.00 AC: 0 AN: 18904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2528

European-Non Finnish (NFE) AF: 0.0000103 AC: 9 AN: 873626

Other (OTH) AF: 0.00 AC: 0 AN: 38176

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147538 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 71850

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000244 AC: 1 AN: 40912

American (AMR) AF: 0.00 AC: 0 AN: 14884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66284

Other (OTH) AF: 0.00 AC: 0 AN: 2028

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=170/30	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs538539239; hg19: chr10-120789812;