Genetic Variant NM_199044.4:c.*1216T>C (chr1-46363062-T-C) – 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.*1216T>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 0.224 in 151,926 control chromosomes in the GnomAD database, including 4,275 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 0.22 ( 4274 hom., cov: 31)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

NSUN4
NM_199044.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0430

Publications

11 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 (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 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.*1216T>C	3_prime_UTR	Exon 6 of 6	NP_950245.2
NSUN4	NM_001387265.1		c.*1216T>C	3_prime_UTR	Exon 6 of 6	NP_001374194.1
NSUN4	NM_001387267.1		c.*1216T>C	3_prime_UTR	Exon 6 of 6	NP_001374196.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NSUN4	ENST00000474844.6	TSL:1 MANE Select	c.*1216T>C	3_prime_UTR	Exon 6 of 6	ENSP00000419740.1	Q96CB9-1
NSUN4	ENST00000307089.7	TSL:1	n.*1760T>C	non_coding_transcript_exon	Exon 5 of 5	ENSP00000471937.1	M0R1K5
NSUN4	ENST00000307089.7	TSL:1	n.*1760T>C	3_prime_UTR	Exon 5 of 5	ENSP00000471937.1	M0R1K5

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33982

AN:

151802

Hom.:

4274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.0204

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.221

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.224

AC:

33977

AN:

151920

Hom.:

4274

Cov.:

AF XY:

0.219

AC XY:

16257

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.148

AC:

6132

AN:

41448

American (AMR)

AF:

0.186

AC:

2834

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

651

AN:

3460

East Asian (EAS)

AF:

0.0206

AC:

107

AN:

5188

South Asian (SAS)

AF:

0.108

AC:

519

AN:

4818

European-Finnish (FIN)

AF:

0.309

AC:

3245

AN:

10500

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19750

AN:

67948

Other (OTH)

AF:

0.217

AC:

456

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1245

2489

3734

4978

6223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.250

Hom.:

1323

Bravo

AF:

0.215

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

-0.96

CADD

Benign

2.8

(source)

DANN

Benign

0.67

PhyloP100

-0.043

Splicing

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