rs587777768

Variant names:

• chr10-119030627-CG-TA
• rs587777768
• NM_199461.4:c.826_827delCGinsTA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_199461.4(NANOS1):​c.826_827delCGinsTA​(p.Arg276Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NANOS1 NM_199461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 3 publications found

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]

NANOS1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 12

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOS1	NM_199461.4	c.826_827delCGinsTA	p.Arg276Tyr	missense_variant		ENST00000425699.3	NP_955631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANOS1	ENST00000425699.3	c.826_827delCGinsTA	p.Arg276Tyr	missense_variant		6	NM_199461.4	ENSP00000393275.1
NANOS1	ENST00000340087.5	c.202_203delCGinsTA	p.Arg68Tyr	missense_variant		6		ENSP00000345924.5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777768; hg19: chr10-120790139;