chr1-46341925-G-T

Variant names:

• chr1-46341925-G-T
• rs10489770
• NM_199044.4:c.93+1006G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000474844.6(NSUN4):​c.93+1006G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000925 in 1,080,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: NSUN4 ENST00000474844.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.429497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474844.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN4	NM_199044.4	MANE Select	c.93+1006G>T		intron	N/A	NP_950245.2
	NSUN4	NR_170618.1		n.716G>T		non_coding_transcript_exon	Exon 2 of 8
	NSUN4	NM_001387265.1		c.93+1006G>T		intron	N/A	NP_001374194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN4	ENST00000474844.6	TSL:1 MANE Select	c.93+1006G>T		intron	N/A	ENSP00000419740.1
	NSUN4	ENST00000307089.7	TSL:1	n.93+1006G>T		intron	N/A	ENSP00000471937.1
	NSUN4	ENST00000498008.5	TSL:2	c.82G>T	p.Gly28*	stop_gained	Exon 1 of 6	ENSP00000478740.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.25e-7 AC: 1 AN: 1080710 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 510292

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22974

American (AMR) AF: 0.00 AC: 0 AN: 8428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14400

East Asian (EAS) AF: 0.00 AC: 0 AN: 26530

South Asian (SAS) AF: 0.00 AC: 0 AN: 19500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2920

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920420

Other (OTH) AF: 0.0000228 AC: 1 AN: 43816

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.5
DANN	Benign	0.70
FATHMM_MKL	Benign	0.066	N
PhyloP100		0.96
Vest4		0.052
GERP RS		1.2
PromoterAI		-0.0060	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10489770; hg19: chr1-46807597;