rs41534051

Positions:

• chr1-46363062-T-C

Variant summary

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

The NM_199044.4(NSUN4):​c.*1216T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,926 control chromosomes in the GnomAD database, including 4,275 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 (4274 hom., cov: 31)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: NSUN4 NM_199044.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSUN4	NM_199044.4	c.*1216T>C		3_prime_UTR_variant	6/6	ENST00000474844.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSUN4	ENST00000474844.6	c.*1216T>C		3_prime_UTR_variant	6/6	1	NM_199044.4	P1
NSUN4	ENST00000307089.7	c.*1760T>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33982 AN: 151802 Hom.: 4274 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.224 AC: 33977 AN: 151920 Hom.: 4274 Cov.: 31 AF XY: 0.219 AC XY: 16257 AN XY: 74224

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.217

Alfa AF: 0.252 Hom.: 1316

Bravo AF: 0.215

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41534051; hg19: chr1-46828734;