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GeneBe

8-38279664-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_023034.2(NSD3):c.3636C>T(p.Ala1212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,384 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00064 ( 8 hom. )

Consequence

NSD3
NM_023034.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30
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 -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-38279664-G-A is Benign according to our data. Variant chr8-38279664-G-A is described in ClinVar as [Benign]. Clinvar id is 783839.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.3 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (883/152194) while in subpopulation AFR AF= 0.0202 (840/41514). AF 95% confidence interval is 0.0191. There are 3 homozygotes in gnomad4. There are 417 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 878 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NSD3NM_023034.2 linkuse as main transcriptc.3636C>T p.Ala1212= synonymous_variant 21/24 ENST00000317025.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NSD3ENST00000317025.13 linkuse as main transcriptc.3636C>T p.Ala1212= synonymous_variant 21/241 NM_023034.2 P4Q9BZ95-1
NSD3ENST00000527502.5 linkuse as main transcriptc.3603C>T p.Ala1201= synonymous_variant 21/241 Q9BZ95-5
NSD3ENST00000433384.6 linkuse as main transcriptc.3489C>T p.Ala1163= synonymous_variant 20/231 A1Q9BZ95-2
NSD3ENST00000528828.1 linkuse as main transcriptn.547C>T non_coding_transcript_exon_variant 1/41

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00577
AC:
878
AN:
152074
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0202
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.00155
AC:
386
AN:
249396
Hom.:
2
AF XY:
0.00119
AC XY:
161
AN XY:
135310
show subpopulations
Gnomad AFR exome
AF:
0.0210
Gnomad AMR exome
AF:
0.00116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000278
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000883
Gnomad OTH exome
AF:
0.000825
GnomAD4 exome
AF:
0.000638
AC:
932
AN:
1461190
Hom.:
8
Cov.:
30
AF XY:
0.000568
AC XY:
413
AN XY:
726878
show subpopulations
Gnomad4 AFR exome
AF:
0.0207
Gnomad4 AMR exome
AF:
0.00134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.0000928
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000621
Gnomad4 OTH exome
AF:
0.00131
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00580
AC:
883
AN:
152194
Hom.:
3
Cov.:
32
AF XY:
0.00560
AC XY:
417
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0202
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00358
Hom.:
1
Bravo
AF:
0.00660
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 03, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
Cadd
Benign
12
Dann
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs115624738; hg19: chr8-38137182; API