10-119029901-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_199461.4(NANOS1):c.100C>A(p.Pro34Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 1,386,522 control chromosomes in the GnomAD database, including 1,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.036 (145 hom., cov: 32)
  • Exomes 𝑓: 0.049 (1678 hom.)
• Consequence: NANOS1 NM_199461.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.977

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022182167).
• BP6: Variant 10-119029901-C-A is Benign according to our data. Variant chr10-119029901-C-A is described in ClinVar as [Benign]. Clinvar id is 1233504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANOS1	NM_199461.4	c.100C>A	p.Pro34Thr	missense_variant	1/1	ENST00000425699.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANOS1	ENST00000425699.3	c.100C>A	p.Pro34Thr	missense_variant	1/1		NM_199461.4	P1

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5468 AN: 150876 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.00865

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0324

GnomAD3 exomes AF: 0.0357 AC: 2394 AN: 67060 Hom.: 68 AF XY: 0.0366 AC XY: 1427 AN XY: 38980

Gnomad AFR exome AF: 0.00623

Gnomad AMR exome AF: 0.0131

Gnomad ASJ exome AF: 0.0229

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0295

Gnomad FIN exome AF: 0.0772

Gnomad NFE exome AF: 0.0511

Gnomad OTH exome AF: 0.0306

GnomAD4 exome AF: 0.0489 AC: 60418 AN: 1235536 Hom.: 1678 Cov.: 32 AF XY: 0.0483 AC XY: 29321 AN XY: 607036

Gnomad4 AFR exome AF: 0.00573

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.0000373

Gnomad4 SAS exome AF: 0.0293

Gnomad4 FIN exome AF: 0.0760

Gnomad4 NFE exome AF: 0.0536

Gnomad4 OTH exome AF: 0.0393

GnomAD4 genome AF: 0.0362 AC: 5467 AN: 150986 Hom.: 145 Cov.: 32 AF XY: 0.0368 AC XY: 2718 AN XY: 73782

Gnomad4 AFR AF: 0.00863

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.0548

Gnomad4 OTH AF: 0.0320

Alfa AF: 0.0467 Hom.: 27

Bravo AF: 0.0302

ExAC AF: 0.0135 AC: 498

Asia WGS AF: 0.0130 AC: 44 AN: 3408

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

GeneDx

Jul 15, 2020

This variant is associated with the following publications: (PMID: 32155011) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	19
Dann	Benign	0.95
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.056
Sift	Uncertain	0.010	D
Sift4G	Benign	0.12	T
Polyphen		0.59	P
Vest4		0.043
ClinPred		0.0071	T
GERP RS		3.6
Varity_R		0.13
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs191267549; hg19: chr10-120789413;