10-119030300-CCCGCCGCCGCCG-CCCGCCGCCG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4_Supporting PP5 BS2

The NM_199461.4(NANOS1):c.517_519del(p.Ala173del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,137,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (0 hom.)
• Consequence: NANOS1 NM_199461.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.46

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_199461.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 10-119030300-CCCG-C is Pathogenic according to our data. Variant chr10-119030300-CCCG-C is described in ClinVar as [Pathogenic]. Clinvar id is 65391.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANOS1	NM_199461.4	c.517_519del	p.Ala173del	inframe_deletion	1/1	ENST00000425699.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANOS1	ENST00000425699.3	c.517_519del	p.Ala173del	inframe_deletion	1/1		NM_199461.4	P1

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 40 AN: 147534 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000202

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000786

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000438

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00813 AC: 4 AN: 492 Hom.: 0 AF XY: 0.0110 AC XY: 3 AN XY: 272

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00824

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00163 AC: 1614 AN: 989464 Hom.: 0 AF XY: 0.00183 AC XY: 856 AN XY: 466718

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.00776

Gnomad4 ASJ exome AF: 0.00426

Gnomad4 EAS exome AF: 0.00670

Gnomad4 SAS exome AF: 0.000215

Gnomad4 FIN exome AF: 0.00848

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.00259

GnomAD4 genome AF: 0.000271 AC: 40 AN: 147630 Hom.: 0 Cov.: 32 AF XY: 0.000250 AC XY: 18 AN XY: 71952

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.000201

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000786

Gnomad4 NFE AF: 0.000438

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 12 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs538539239; hg19: chr10-120789812;