Variant 8-38304635-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_023034.2(NSD3):c.2563A>G(p.Ser855Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000804 in 1,613,788 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 19 hom. )

Consequence

NSD3
NM_023034.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.99

Variant links:

Genes affected

NSD3 (HGNC:12767): (nuclear receptor binding SET domain protein 3) This gene is related to the Wolf-Hirschhorn syndrome candidate-1 gene and encodes a protein with PWWP (proline-tryptophan-tryptophan-proline) domains. This protein methylates histone H3 at lysine residues 4 and 27, which represses gene transcription. Two alternatively spliced variants have been described. [provided by RefSeq, May 2015]

NSD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032746494).

BP6

Variant 8-38304635-T-C is Benign according to our data. Variant chr8-38304635-T-C is described in ClinVar as [Benign]. Clinvar id is 733352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSD3	NM_023034.2 linkuse as main transcript	c.2563A>G	p.Ser855Gly	missense_variant	14/24	ENST00000317025.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSD3	ENST00000317025.13 linkuse as main transcript	c.2563A>G	p.Ser855Gly	missense_variant	14/24	1	NM_023034.2	P4	Q9BZ95-1
NSD3	ENST00000527502.5 linkuse as main transcript	c.2563A>G	p.Ser855Gly	missense_variant	14/24	1			Q9BZ95-5
NSD3	ENST00000433384.6 linkuse as main transcript	c.2563A>G	p.Ser855Gly	missense_variant	14/23	1		A1	Q9BZ95-2

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00169

AC:

421

AN:

249016

Hom.:

AF XY:

0.00223

AC XY:

301

AN XY:

135126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000833

AC:

1218

AN:

1461460

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

881

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.000525

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0162

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.00177

AC:

214

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.85

L;L;L

MutationTaster

Benign

0.76

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.48

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.10

MutPred

0.30

Loss of stability (P = 0.0326);Loss of stability (P = 0.0326);Loss of stability (P = 0.0326);

MVP

0.20

MPC

0.40

ClinPred

0.049

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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