10-119030300-CCCGCCGCCGCCG-CCCG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_199461.4(NANOS1):c.511_519del(p.Ala171_Ala173del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 1,154,190 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (2 hom.)
• Consequence: NANOS1 NM_199461.4 inframe_deletion
• Clinical Significance: Likely 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 Likely_benign. Variant got -4 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 id is 3042603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANOS1	NM_199461.4	c.511_519del	p.Ala171_Ala173del	inframe_deletion	1/1	ENST00000425699.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANOS1	ENST00000425699.3	c.511_519del	p.Ala171_Ala173del	inframe_deletion	1/1		NM_199461.4	P1

Frequencies

GnomAD3 genomes AF: 0.000596 AC: 88 AN: 147534 Hom.: 0 Cov.: 32

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

GnomAD4 exome AF: 0.000610 AC: 614 AN: 1006554 Hom.: 2 AF XY: 0.000630 AC XY: 299 AN XY: 474866

Gnomad4 AFR exome AF: 0.0000997

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.000686

Gnomad4 SAS exome AF: 0.0000529

Gnomad4 FIN exome AF: 0.000519

Gnomad4 NFE exome AF: 0.000603

Gnomad4 OTH exome AF: 0.000733

GnomAD4 genome AF: 0.000596 AC: 88 AN: 147636 Hom.: 0 Cov.: 32 AF XY: 0.000695 AC XY: 50 AN XY: 71960

Gnomad4 AFR AF: 0.000317

Gnomad4 AMR AF: 0.000201

Gnomad4 ASJ AF: 0.00265

Gnomad4 EAS AF: 0.000591

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.000679

Gnomad4 OTH AF: 0.000976

Bravo AF: 0.000589

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NANOS1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 19, 2023

This variant is classified as likely 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;