chr10-119029751-G-C

Position:

• chr10-119029751-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_199461.4(NANOS1):​c.-51G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 960,190 control chromosomes in the GnomAD database, including 83,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8498 hom., cov: 30)
  • Exomes 𝑓: 0.42 (74531 hom.)
• Consequence: NANOS1 NM_199461.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.14

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-119029751-G-C is Benign according to our data. Variant chr10-119029751-G-C is described in ClinVar as [Benign]. Clinvar id is 1268518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NANOS1	NM_199461.4	c.-51G>C		5_prime_UTR_variant	1/1	ENST00000425699.3	NP_955631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NANOS1	ENST00000425699	c.-51G>C		5_prime_UTR_variant	1/1		NM_199461.4	ENSP00000393275.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 46937 AN: 145464 Hom.: 8500 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.307

GnomAD3 exomes AF: 0.385 AC: 47 AN: 122 Hom.: 11 AF XY: 0.338 AC XY: 27 AN XY: 80

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.424 AC: 345094 AN: 814626 Hom.: 74531 Cov.: 15 AF XY: 0.424 AC XY: 159867 AN XY: 377068

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.322 AC: 46933 AN: 145564 Hom.: 8498 Cov.: 30 AF XY: 0.322 AC XY: 22827 AN XY: 70806

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.307

Alfa AF: 0.368 Hom.: 1351

Bravo AF: 0.315

Asia WGS AF: 0.290 AC: 648 AN: 2230

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	18
DANN	Benign	0.71

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: rs186808650; hg19: chr10-120789263;