rs12075550

Variant names:

• chr1-46368540-T-C
• rs12075550
• NM_001387266.1:c.*671T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387266.1(NSUN4):​c.*671T>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 0.393 in 151,958 control chromosomes in the GnomAD database, including 11,835 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 0.39 (11835 hom., cov: 32)
• Consequence: NSUN4 NM_001387266.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387266.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN4	NM_001387266.1		c.*671T>C		3_prime_UTR	Exon 7 of 7	NP_001374195.1
	NSUN4	NM_001387269.1		c.*152T>C		3_prime_UTR	Exon 7 of 7	NP_001374198.1
	NSUN4	NM_001387268.1		c.1006-232T>C		intron	N/A	NP_001374197.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN4	ENST00000718455.1		c.607-232T>C		intron	N/A	ENSP00000520833.1	A0ABB0MVH8

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59671 AN: 151840 Hom.: 11813 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59723 AN: 151958 Hom.: 11835 Cov.: 32 AF XY: 0.393 AC XY: 29171 AN XY: 74270

African (AFR) AF: 0.399 AC: 16538 AN: 41440

American (AMR) AF: 0.314 AC: 4790 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3466

East Asian (EAS) AF: 0.327 AC: 1693 AN: 5172

South Asian (SAS) AF: 0.501 AC: 2414 AN: 4822

European-Finnish (FIN) AF: 0.383 AC: 4037 AN: 10544

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27871 AN: 67950

Other (OTH) AF: 0.397 AC: 839 AN: 2112

Alfa AF: 0.382 Hom.: 1418

Bravo AF: 0.385

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs12075550; hg19: chr1-46834212;