Variant 8-38290632-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_023034.2(NSD3):c.2961C>T(p.Asn987=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000614 in 1,613,962 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00098 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 7 hom. )

Consequence

NSD3
NM_023034.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.72

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 8-38290632-G-A is Benign according to our data. Variant chr8-38290632-G-A is described in ClinVar as [Benign]. Clinvar id is 713975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 149 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSD3	NM_023034.2 linkuse as main transcript	c.2961C>T	p.Asn987=	synonymous_variant	17/24	ENST00000317025.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSD3	ENST00000317025.13 linkuse as main transcript	c.2961C>T	p.Asn987=	synonymous_variant	17/24	1	NM_023034.2	P4	Q9BZ95-1
NSD3	ENST00000527502.5 linkuse as main transcript	c.2961C>T	p.Asn987=	synonymous_variant	17/24	1			Q9BZ95-5
NSD3	ENST00000433384.6 linkuse as main transcript	c.2814C>T	p.Asn938=	synonymous_variant	16/23	1		A1	Q9BZ95-2
NSD3	ENST00000526050.1 linkuse as main transcript	n.117C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

148

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00240

AC:

599

AN:

249270

Hom.:

AF XY:

0.00183

AC XY:

247

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.000576

AC:

842

AN:

1461664

Hom.:

Cov.:

AF XY:

0.000509

AC XY:

370

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000978

AC:

149

AN:

152298

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000474

Hom.:

Bravo

AF:

0.00155

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 22, 2018	- -

NSD3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.8

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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