dbSNP rs10489769: NSUN4:c.93+112A>G (chr1-46341031-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199044.4(NSUN4):c.93+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,168,154 control chromosomes in the GnomAD database, including 42,190 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 0.23 ( 4412 hom., cov: 31)

Exomes 𝑓: 0.26 ( 37778 hom. )

Consequence

NSUN4
NM_199044.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.611

Publications

24 publications found

Variant links:

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]

NSUN4 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199044.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NSUN4	NM_199044.4	MANE Select	c.93+112A>G	intron	N/A	NP_950245.2
NSUN4	NM_001387265.1		c.93+112A>G	intron	N/A	NP_001374194.1
NSUN4	NM_001387266.1		c.93+112A>G	intron	N/A	NP_001374195.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NSUN4	ENST00000474844.6	TSL:1 MANE Select	c.93+112A>G	intron	N/A	ENSP00000419740.1
NSUN4	ENST00000307089.7	TSL:1	n.93+112A>G	intron	N/A	ENSP00000471937.1
NSUN4	ENST00000469918.5	TSL:3	n.93+112A>G	intron	N/A	ENSP00000478949.1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34587

AN:

151898

Hom.:

4412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0172

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.261

AC:

264908

AN:

1016138

Hom.:

37778

Cov.:

AF XY:

0.256

AC XY:

129699

AN XY:

505762

show subpopulations

African (AFR)

AF:

0.145

AC:

3348

AN:

23080

American (AMR)

AF:

0.144

AC:

3293

AN:

22864

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

3376

AN:

17714

East Asian (EAS)

AF:

0.0109

AC:

359

AN:

33072

South Asian (SAS)

AF:

0.108

AC:

6478

AN:

60146

European-Finnish (FIN)

AF:

0.302

AC:

13218

AN:

43728

Middle Eastern (MID)

AF:

0.188

AC:

862

AN:

4580

European-Non Finnish (NFE)

AF:

0.292

AC:

223641

AN:

766258

Other (OTH)

AF:

0.231

AC:

10333

AN:

44696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

8907

17814

26720

35627

44534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6680

13360

20040

26720

33400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.227

AC:

34582

AN:

152016

Hom.:

4412

Cov.:

AF XY:

0.223

AC XY:

16562

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.155

AC:

6449

AN:

41482

American (AMR)

AF:

0.189

AC:

2880

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

656

AN:

3470

East Asian (EAS)

AF:

0.0174

AC:

AN:

5166

South Asian (SAS)

AF:

0.103

AC:

495

AN:

4816

European-Finnish (FIN)

AF:

0.312

AC:

3296

AN:

10556

Middle Eastern (MID)

AF:

0.253

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.294

AC:

19966

AN:

67940

Other (OTH)

AF:

0.221

AC:

466

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1339

2678

4017

5356

6695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.258

Hom.:

3701

Bravo

AF:

0.219

Asia WGS

AF:

0.0760

AC:

266

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.4

(source)

DANN

Benign

0.58

PhyloP100

-0.61

PromoterAI

-0.059

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over