10-119030082-GGGCGCTGGGGCC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4 BP6_Very_Strong BS2

The NM_199461.4(NANOS1):c.295_306del(p.Ala99_Pro102del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,316,104 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (7 hom.)
• Consequence: NANOS1 NM_199461.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.75

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 -10 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_199461.4.
• BP6: Variant 10-119030082-GGGCGCTGGGGCC-G is Benign according to our data. Variant chr10-119030082-GGGCGCTGGGGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2498471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 509 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANOS1	NM_199461.4	c.295_306del	p.Ala99_Pro102del	inframe_deletion	1/1	ENST00000425699.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANOS1	ENST00000425699.3	c.295_306del	p.Ala99_Pro102del	inframe_deletion	1/1		NM_199461.4	P1

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 509 AN: 150478 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.00377

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000401

Gnomad OTH AF: 0.00193

GnomAD3 exomes AF: 0.000366 AC: 1 AN: 2732 Hom.: 0 AF XY: 0.000592 AC XY: 1 AN XY: 1690

Gnomad AFR exome AF: 0.0109

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.000710 AC: 828 AN: 1165518 Hom.: 7 AF XY: 0.000691 AC XY: 391 AN XY: 565704

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.000436

Gnomad4 ASJ exome AF: 0.00483

Gnomad4 EAS exome AF: 0.000149

Gnomad4 SAS exome AF: 0.000781

Gnomad4 FIN exome AF: 0.000265

Gnomad4 NFE exome AF: 0.000326

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00338 AC: 509 AN: 150586 Hom.: 2 Cov.: 32 AF XY: 0.00328 AC XY: 241 AN XY: 73532

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.00191

Gnomad4 ASJ AF: 0.00377

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000101

Gnomad4 NFE AF: 0.000401

Gnomad4 OTH AF: 0.00191

Alfa AF: 0.0000543 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

NANOS1: BS1 -

NANOS1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 21, 2019

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: rs762815077; hg19: chr10-120789594;