rs1488935

Variant names:

• chr8-38276275-G-A
• rs1488935
• NM_023034.2:c.4072+21C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-38276275-G-A
• chr8-38276275-G-C
• chr8-38276275-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 20 publications found

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]

ENSG00000255487 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NSD3	NM_023034.2	c.4072+21C>T		intron_variant	Intron 23 of 23	ENST00000317025.13	NP_075447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSD3	ENST00000317025.13	c.4072+21C>T		intron_variant	Intron 23 of 23	1	NM_023034.2	ENSP00000313983.7

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32583 AN: 152034 Hom.: 3692 Cov.: 32

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

GnomAD2 exomes AF: 0.207 AC: 51195 AN: 246750 AF XY: 0.201

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 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

African (AFR) AF: 0.204 AC: 6814 AN: 33448

American (AMR) AF: 0.231 AC: 10244 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3590 AN: 26082

East Asian (EAS) AF: 0.314 AC: 12460 AN: 39652

South Asian (SAS) AF: 0.117 AC: 10033 AN: 85918

European-Finnish (FIN) AF: 0.181 AC: 9654 AN: 53360

Middle Eastern (MID) AF: 0.178 AC: 978 AN: 5492

European-Non Finnish (NFE) AF: 0.230 AC: 255019 AN: 1109976

Other (OTH) AF: 0.215 AC: 12979 AN: 60282

GnomAD4 genome AF: 0.215 AC: 32642 AN: 152152 Hom.: 3707 Cov.: 32 AF XY: 0.210 AC XY: 15594 AN XY: 74388

African (AFR) AF: 0.209 AC: 8694 AN: 41504

American (AMR) AF: 0.226 AC: 3452 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3466

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5168

South Asian (SAS) AF: 0.110 AC: 528 AN: 4818

European-Finnish (FIN) AF: 0.183 AC: 1939 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15131 AN: 67992

Other (OTH) AF: 0.214 AC: 451 AN: 2110

Alfa AF: 0.216 Hom.: 14431

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
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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