Variant chr3-47101597-AGTGT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_014159.7(SETD2):c.4918-46_4918-43del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 726,374 control chromosomes in the GnomAD database, including 355 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.039 ( 219 hom., cov: 0)

Exomes 𝑓: 0.041 ( 136 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.996

Variant links:

Genes affected

SETD2 (HGNC:18420): (SET domain containing 2, histone lysine methyltransferase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein belonging to a class of huntingtin interacting proteins characterized by WW motifs. This protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [provided by RefSeq, Aug 2008]

SETD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 3-47101597-AGTGT-A is Benign according to our data. Variant chr3-47101597-AGTGT-A is described in ClinVar as [Benign]. Clinvar id is 1292847.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD2	NM_014159.7 linkuse as main transcript	c.4918-46_4918-43del		intron_variant		ENST00000409792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD2	ENST00000409792.4 linkuse as main transcript	c.4918-46_4918-43del		intron_variant		5	NM_014159.7	P3	Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5495

AN:

141484

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00229

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0319

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.0608

Gnomad FIN

AF:

0.0206

Gnomad MID

AF:

0.0493

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0300

GnomAD3 exomes

AF:

0.0693

AC:

8462

AN:

122034

Hom.:

125

AF XY:

0.0674

AC XY:

4468

AN XY:

66322

show subpopulations

Gnomad AFR exome

AF:

0.0535

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.0449

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.0643

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0474

Gnomad OTH exome

AF:

0.0525

GnomAD4 exome

AF:

0.0413

AC:

24160

AN:

584792

Hom.:

136

AF XY:

0.0414

AC XY:

12903

AN XY:

311624

show subpopulations

Gnomad4 AFR exome

AF:

0.0353

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.0387

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.0453

Gnomad4 FIN exome

AF:

0.0396

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0408

GnomAD4 genome

AF:

0.0389

AC:

5501

AN:

141582

Hom.:

219

Cov.:

AF XY:

0.0421

AC XY:

2887

AN XY:

68638

show subpopulations

Gnomad4 AFR

AF:

0.0259

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.0319

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.0609

Gnomad4 FIN

AF:

0.0206

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0302

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 submitter

clinical testing

GeneDx

Sep 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

4.0

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