NM_023034.2:c.3867+412A>G

Variant names:

• chr8-38277894-T-C
• rs7845911
• NM_023034.2:c.3867+412A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023034.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSD3	NM_023034.2	MANE Select	c.3867+412A>G		intron	N/A	NP_075447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSD3	ENST00000317025.13	TSL:1 MANE Select	c.3867+412A>G		intron	N/A	ENSP00000313983.7
	NSD3	ENST00000527502.5	TSL:1	c.3834+412A>G		intron	N/A	ENSP00000434730.1
	NSD3	ENST00000433384.6	TSL:1	c.3720+412A>G		intron	N/A	ENSP00000393284.2

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

African (AFR) AF: 0.207 AC: 8584 AN: 41380

American (AMR) AF: 0.217 AC: 3308 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1577 AN: 5152

South Asian (SAS) AF: 0.0923 AC: 443 AN: 4802

European-Finnish (FIN) AF: 0.182 AC: 1910 AN: 10482

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14635 AN: 67922

Other (OTH) AF: 0.203 AC: 428 AN: 2110

Alfa AF: 0.212 Hom.: 4336

Bravo AF: 0.219

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.041
DANN	Benign	0.49
PhyloP100		-1.3
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: rs7845911; hg19: chr8-38135412;