chr8-38276275-G-A

Position:

• chr8-38276275-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

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
NSD3	NM_023034.2	c.4072+21C>T		intron_variant		ENST00000317025.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSD3	ENST00000317025.13	c.4072+21C>T		intron_variant		1	NM_023034.2	P4
	ENST00000529325.1	n.37-186G>A		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.207 AC: 51195 AN: 246750 Hom.: 5503 AF XY: 0.201 AC XY: 26907 AN XY: 133780

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

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

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

Other links and lift over

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