5-74767425-T-C

Position:

• chr5-74767425-T-C

Variant summary

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

The NM_014886.6(NSA2):​c.3+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,598,790 control chromosomes in the GnomAD database, including 12,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1498 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11379 hom.)
• Consequence: NSA2 NM_014886.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.714

Genes affected

NSA2 (HGNC:30728): (NSA2 ribosome biogenesis factor) This gene encodes a nucleolar protein involved in cell cycle regulation and proliferation. This gene was identified based on sequence similarity to a highly conserved Saccharomyces cerevisiae gene encoding a pre-ribosomal protein, which is involved in large ribosomal subunit biogenesis. The encoded protein is found at elevated levels in diabetic nephropathy. Alternative splicing results in multiple transcript variants. Several related pseudogenes have been identified. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-74767425-T-C is Benign according to our data. Variant chr5-74767425-T-C is described in ClinVar as [Benign]. Clinvar id is 1234496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSA2	NM_014886.6	c.3+62T>C		intron_variant		ENST00000610426.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSA2	ENST00000610426.5	c.3+62T>C		intron_variant		1	NM_014886.6	P1
NSA2	ENST00000296802.9	c.3+62T>C		intron_variant		5
NSA2	ENST00000513356.1	n.101+62T>C		intron_variant, non_coding_transcript_variant		3
NSA2	ENST00000514918.5	n.116+62T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20420 AN: 152028 Hom.: 1498 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.121 AC: 175571 AN: 1446644 Hom.: 11379 AF XY: 0.121 AC XY: 87358 AN XY: 719332

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0907

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.0157

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.134 AC: 20425 AN: 152146 Hom.: 1498 Cov.: 32 AF XY: 0.134 AC XY: 9945 AN XY: 74412

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.148

Alfa AF: 0.129 Hom.: 173

Bravo AF: 0.139

Asia WGS AF: 0.0720 AC: 251 AN: 3478

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

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.0
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116165962; hg19: chr5-74063250;