5-177212104-T-C

Position:

chr5-177212104-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022455.5(NSD1):c.3705T>C(p.Asn1235Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 1,613,878 control chromosomes in the GnomAD database, including 4,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1321 hom., cov: 31)

Exomes 𝑓: 0.056 ( 3271 hom. )

Consequence

NSD1
NM_022455.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.158

Variant links:

Genes affected

NSD1 (HGNC:14234): (nuclear receptor binding SET domain protein 1) This gene encodes a protein containing a SET domain, 2 LXXLL motifs, 3 nuclear translocation signals (NLSs), 4 plant homeodomain (PHD) finger regions, and a proline-rich region. The encoded protein enhances androgen receptor (AR) transactivation, and this enhancement can be increased further in the presence of other androgen receptor associated coregulators. This protein may act as a nucleus-localized, basic transcriptional factor and also as a bifunctional transcriptional regulator. Mutations of this gene have been associated with Sotos syndrome and Weaver syndrome. One version of childhood acute myeloid leukemia is the result of a cryptic translocation with the breakpoints occurring within nuclear receptor-binding Su-var, enhancer of zeste, and trithorax domain protein 1 on chromosome 5 and nucleoporin, 98-kd on chromosome 11. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Sep 2018]

NSD1 links:

NSD1 (HGNC:):

NSD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 5-177212104-T-C is Benign according to our data. Variant chr5-177212104-T-C is described in ClinVar as [Benign]. Clinvar id is 96057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-177212104-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.158 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSD1	NM_022455.5 linkuse as main transcript	c.3705T>C	p.Asn1235Asn	synonymous_variant	5/23	ENST00000439151.7	NP_071900.2	Q96L73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSD1	ENST00000439151.7 linkuse as main transcript	c.3705T>C	p.Asn1235Asn	synonymous_variant	5/23	1	NM_022455.5	ENSP00000395929.2		Q96L73-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15427

AN:

151886

Hom.:

1319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0693

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.0866

Gnomad FIN

AF:

0.0275

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0486

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0640

AC:

16102

AN:

251432

Hom.:

901

AF XY:

0.0633

AC XY:

8601

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.0398

Gnomad ASJ exome

AF:

0.0587

Gnomad EAS exome

AF:

0.0191

Gnomad SAS exome

AF:

0.0955

Gnomad FIN exome

AF:

0.0318

Gnomad NFE exome

AF:

0.0507

Gnomad OTH exome

AF:

0.0671

GnomAD4 exome

AF:

0.0564

AC:

82437

AN:

1461874

Hom.:

3271

Cov.:

AF XY:

0.0572

AC XY:

41577

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.0436

Gnomad4 ASJ exome

AF:

0.0584

Gnomad4 EAS exome

AF:

0.0171

Gnomad4 SAS exome

AF:

0.0934

Gnomad4 FIN exome

AF:

0.0338

Gnomad4 NFE exome

AF:

0.0498

Gnomad4 OTH exome

AF:

0.0680

GnomAD4 genome

AF:

0.102

AC:

15446

AN:

152004

Hom.:

1321

Cov.:

AF XY:

0.0985

AC XY:

7320

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.0692

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.0869

Gnomad4 FIN

AF:

0.0275

Gnomad4 NFE

AF:

0.0487

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0649

Hom.:

315

Bravo

AF:

0.110

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

EpiCase

AF:

0.0516

EpiControl

AF:

0.0540

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 23, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Sotos syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 03, 2022	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.0

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over