Variant chr1-46345057-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_199044.4(NSUN4):c.350C>A(p.Ala117Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000685 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 0 hom. )

Consequence

NSUN4
NM_199044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.460

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055049837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSUN4	NM_199044.4 linkuse as main transcript	c.350C>A	p.Ala117Asp	missense_variant	2/6	ENST00000474844.6	NP_950245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN4	ENST00000474844.6 linkuse as main transcript	c.350C>A	p.Ala117Asp	missense_variant	2/6	1	NM_199044.4	ENSP00000419740	P1	Q96CB9-1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000298

AC:

AN:

251388

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000722

AC:

1055

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000667

AC XY:

485

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000918

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000329

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000706

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.350C>A (p.A117D) alteration is located in exon 2 (coding exon 2) of the NSUN4 gene. This alteration results from a C to A substitution at nucleotide position 350, causing the alanine (A) at amino acid position 117 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.0

DANN

Benign

0.92

DEOGEN2

Benign

0.00071

T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.050

N;N

REVEL

Benign

0.15

Sift

Benign

0.51

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.21

B;.

Vest4

0.25

MVP

0.29

MPC

0.41

ClinPred

0.0091

GERP RS

2.4

Varity_R

0.13

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over