10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BS1 BS2

The NM_199461.4(NANOS1):c.517_519dup(p.Ala173dup) variant causes a 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: NANOS1 NM_199461.4 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B: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 Benign. Variant got -9 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 id is 3049116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome 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 gnomad4_exome. There are 629 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 685 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANOS1	NM_199461.4	c.517_519dup	p.Ala173dup	inframe_insertion	1/1	ENST00000425699.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANOS1	ENST00000425699.3	c.517_519dup	p.Ala173dup	inframe_insertion	1/1		NM_199461.4	P1

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 685 AN: 147534 Hom.: 3 Cov.: 32

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

GnomAD3 exomes AF: 0.00203 AC: 1 AN: 492 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 272

Gnomad AFR exome AF: 0.00

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: 0.00275

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00139 AC: 1403 AN: 1006542 Hom.: 3 Cov.: 32 AF XY: 0.00132 AC XY: 629 AN XY: 474864

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0170

Gnomad4 SAS exome AF: 0.00227

Gnomad4 FIN exome AF: 0.000173

Gnomad4 NFE exome AF: 0.000806

Gnomad4 OTH exome AF: 0.00155

GnomAD4 genome AF: 0.00467 AC: 690 AN: 147636 Hom.: 3 Cov.: 32 AF XY: 0.00452 AC XY: 325 AN XY: 71962

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.00154

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000449

Gnomad4 NFE AF: 0.000739

Gnomad4 OTH AF: 0.00293

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NANOS1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 14, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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;