rs17361749

Positions:

• chr1-46340808-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199044.4(NSUN4):​c.-19C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,599,658 control chromosomes in the GnomAD database, including 59,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4266 hom., cov: 31)
  • Exomes 𝑓: 0.27 (55525 hom.)
• Consequence: NSUN4 NM_199044.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

Genes affected

NSUN4 (HGNC:31802): (NOP2/Sun RNA methyltransferase 4) Enables rRNA (cytosine-C5-)-methyltransferase activity. Involved in rRNA methylation. Part of mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSUN4	NM_199044.4	c.-19C>T		5_prime_UTR_variant	1/6	ENST00000474844.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSUN4	ENST00000474844.6	c.-19C>T		5_prime_UTR_variant	1/6	1	NM_199044.4	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33625 AN: 152072 Hom.: 4267 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.222

GnomAD3 exomes AF: 0.210 AC: 47867 AN: 228318 Hom.: 6049 AF XY: 0.211 AC XY: 26152 AN XY: 124094

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.0211

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.267 AC: 385965 AN: 1447468 Hom.: 55525 Cov.: 30 AF XY: 0.262 AC XY: 188722 AN XY: 719444

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.0162

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.221 AC: 33619 AN: 152190 Hom.: 4266 Cov.: 31 AF XY: 0.216 AC XY: 16102 AN XY: 74398

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.218

Alfa AF: 0.273 Hom.: 5665

Bravo AF: 0.212

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs17361749; hg19: chr1-46806480;