rs1488935

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023034.2(NSD3):​c.4072+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,610,792 control chromosomes in the GnomAD database, including 40,206 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 0.21 ( 3707 hom., cov: 32)
Exomes 𝑓: 0.22 ( 36499 hom. )

Consequence

NSD3
NM_023034.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NSD3NM_023034.2 linkuse as main transcriptc.4072+21C>T intron_variant ENST00000317025.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NSD3ENST00000317025.13 linkuse as main transcriptc.4072+21C>T intron_variant 1 NM_023034.2 P4Q9BZ95-1
ENST00000529325.1 linkuse as main transcriptn.37-186G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.214
AC:
32583
AN:
152034
Hom.:
3692
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.209
Gnomad AMI
AF:
0.355
Gnomad AMR
AF:
0.225
Gnomad ASJ
AF:
0.138
Gnomad EAS
AF:
0.307
Gnomad SAS
AF:
0.109
Gnomad FIN
AF:
0.183
Gnomad MID
AF:
0.203
Gnomad NFE
AF:
0.223
Gnomad OTH
AF:
0.215
GnomAD3 exomes
AF:
0.207
AC:
51195
AN:
246750
Hom.:
5503
AF XY:
0.201
AC XY:
26907
AN XY:
133780
show subpopulations
Gnomad AFR exome
AF:
0.210
Gnomad AMR exome
AF:
0.233
Gnomad ASJ exome
AF:
0.131
Gnomad EAS exome
AF:
0.316
Gnomad SAS exome
AF:
0.114
Gnomad FIN exome
AF:
0.183
Gnomad NFE exome
AF:
0.219
Gnomad OTH exome
AF:
0.208
GnomAD4 exome
AF:
0.221
AC:
321771
AN:
1458640
Hom.:
36499
Cov.:
31
AF XY:
0.217
AC XY:
157241
AN XY:
725436
show subpopulations
Gnomad4 AFR exome
AF:
0.204
Gnomad4 AMR exome
AF:
0.231
Gnomad4 ASJ exome
AF:
0.138
Gnomad4 EAS exome
AF:
0.314
Gnomad4 SAS exome
AF:
0.117
Gnomad4 FIN exome
AF:
0.181
Gnomad4 NFE exome
AF:
0.230
Gnomad4 OTH exome
AF:
0.215
GnomAD4 genome
AF:
0.215
AC:
32642
AN:
152152
Hom.:
3707
Cov.:
32
AF XY:
0.210
AC XY:
15594
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.209
Gnomad4 AMR
AF:
0.226
Gnomad4 ASJ
AF:
0.138
Gnomad4 EAS
AF:
0.307
Gnomad4 SAS
AF:
0.110
Gnomad4 FIN
AF:
0.183
Gnomad4 NFE
AF:
0.223
Gnomad4 OTH
AF:
0.214
Alfa
AF:
0.212
Hom.:
6260
Bravo
AF:
0.224
Asia WGS
AF:
0.205
AC:
713
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
12
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs1488935; hg19: chr8-38133793; COSMIC: COSV57667817; COSMIC: COSV57667817; API