8-38277894-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023034.2(NSD3):c.3867+412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,766 control chromosomes in the GnomAD database, including 3,530 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 (3530 hom., cov: 31)
• Consequence: NSD3 NM_023034.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• 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.3867+412A>G		intron_variant		ENST00000317025.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSD3	ENST00000317025.13	c.3867+412A>G		intron_variant		1	NM_023034.2	P4
NSD3	ENST00000433384.6	c.3720+412A>G		intron_variant		1		A1
NSD3	ENST00000527502.5	c.3834+412A>G		intron_variant		1
NSD3	ENST00000528828.1	n.778+412A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31631 AN: 151664 Hom.: 3514 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31691 AN: 151766 Hom.: 3530 Cov.: 31 AF XY: 0.203 AC XY: 15081 AN XY: 74148

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.0923

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.203

Alfa AF: 0.212 Hom.: 3357

Bravo AF: 0.219

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.041
Dann	Benign	0.49

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: rs7845911; hg19: chr8-38135412;