10-119030300-CCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCG

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.514_519dup(p.Ala172_Ala173dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,154,186 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (2 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 Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_199461.4.
• BP6: Variant 10-119030300-C-CCCGCCG is Benign according to our data. Variant chr10-119030300-C-CCCGCCG is described in ClinVar as [Benign]. Clinvar id is 776547.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 590 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANOS1	NM_199461.4	c.514_519dup	p.Ala172_Ala173dup	inframe_insertion	1/1	ENST00000425699.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANOS1	ENST00000425699.3	c.514_519dup	p.Ala172_Ala173dup	inframe_insertion	1/1		NM_199461.4	P1

Frequencies

GnomAD3 genomes AF: 0.00400 AC: 590 AN: 147534 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000672

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000256

Gnomad OTH AF: 0.000986

GnomAD4 exome AF: 0.000575 AC: 579 AN: 1006550 Hom.: 2 Cov.: 32 AF XY: 0.000583 AC XY: 277 AN XY: 474866

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000211

Gnomad4 SAS exome AF: 0.00714

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000675

Gnomad4 OTH exome AF: 0.00165

GnomAD4 genome AF: 0.00400 AC: 590 AN: 147636 Hom.: 0 Cov.: 32 AF XY: 0.00375 AC XY: 270 AN XY: 71960

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.000671

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000257

Gnomad4 OTH AF: 0.000976

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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;