1-46341925-G-A

Position:

• chr1-46341925-G-A

Variant summary

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

The NM_199044.4(NSUN4):​c.93+1006G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,232,722 control chromosomes in the GnomAD database, including 10,058 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 0.12 (1280 hom., cov: 31)
  • Exomes 𝑓: 0.13 (8778 hom.)
• Consequence: NSUN4 NM_199044.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965

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 (MetaRNN=0.0017829537).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSUN4	NM_199044.4	c.93+1006G>A		intron_variant		ENST00000474844.6	NP_950245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN4	ENST00000474844.6	c.93+1006G>A		intron_variant		1	NM_199044.4	ENSP00000419740	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17967 AN: 151940 Hom.: 1276 Cov.: 31

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.125 AC: 135382 AN: 1080664 Hom.: 8778 Cov.: 35 AF XY: 0.126 AC XY: 64142 AN XY: 510270

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.0747

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.118 AC: 17983 AN: 152058 Hom.: 1280 Cov.: 31 AF XY: 0.124 AC XY: 9189 AN XY: 74308

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.118

Alfa AF: 0.121 Hom.: 1688

Bravo AF: 0.117

TwinsUK AF: 0.117 AC: 434

ALSPAC AF: 0.116 AC: 447

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.0
DANN	Benign	0.72
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0018	T
MutationTaster	Benign	1.0	P;P;P
Sift4G	Benign	0.24	T
Vest4		0.18
MVP		0.54
GERP RS		1.2

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: rs10489770; hg19: chr1-46807597; COSMIC: COSV61062547; COSMIC: COSV61062547;