Genetic Variant NSUN4:c.93+1006G>A (chr1-46341925-G-A) – 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+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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.965

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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+1006G>A	intron	N/A	NP_950245.2
NSUN4	NR_170618.1		n.716G>A	non_coding_transcript_exon	Exon 2 of 8
NSUN4	NM_001387265.1		c.93+1006G>A	intron	N/A	NP_001374194.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NSUN4	ENST00000474844.6	TSL:1 MANE Select	c.93+1006G>A		intron	N/A	ENSP00000419740.1
NSUN4	ENST00000307089.7	TSL:1	n.93+1006G>A		intron	N/A	ENSP00000471937.1
NSUN4	ENST00000498008.5	TSL:2	c.82G>A	p.Gly28Arg	missense	Exon 1 of 6	ENSP00000478740.1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17967

AN:

151940

Hom.:

1276

Cov.:

show subpopulations

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.:

AF XY:

0.126

AC XY:

64142

AN XY:

510270

show subpopulations

African (AFR)

AF:

0.0533

AC:

1225

AN:

22974

American (AMR)

AF:

0.245

AC:

2066

AN:

8428

Ashkenazi Jewish (ASJ)

AF:

0.0747

AC:

1076

AN:

14400

East Asian (EAS)

AF:

0.154

AC:

4077

AN:

26530

South Asian (SAS)

AF:

0.146

AC:

2839

AN:

19500

European-Finnish (FIN)

AF:

0.206

AC:

4470

AN:

21722

Middle Eastern (MID)

AF:

0.101

AC:

295

AN:

2920

European-Non Finnish (NFE)

AF:

0.124

AC:

113798

AN:

920374

Other (OTH)

AF:

0.126

AC:

5536

AN:

43816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

6624

13248

19873

26497

33121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4816

9632

14448

19264

24080

<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:

0.118

AC:

17983

AN:

152058

Hom.:

1280

Cov.:

AF XY:

0.124

AC XY:

9189

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0564

AC:

2340

AN:

41488

American (AMR)

AF:

0.212

AC:

3237

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0790

AC:

274

AN:

3468

East Asian (EAS)

AF:

0.152

AC:

787

AN:

5166

South Asian (SAS)

AF:

0.142

AC:

686

AN:

4818

European-Finnish (FIN)

AF:

0.200

AC:

2113

AN:

10570

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8199

AN:

67968

Other (OTH)

AF:

0.118

AC:

249

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

809

1618

2428

3237

4046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.121

Hom.:

2186

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.0

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.024

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0018

PhyloP100

0.96

Sift4G

Benign

0.24

Vest4

0.18

MVP

0.54

GERP RS

1.2

PromoterAI

0.013

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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