3-47017833-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014159.7(SETD2):c.7432-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 861,096 control chromosomes in the GnomAD database, including 138,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (23454 hom., cov: 32)
  • Exomes 𝑓: 0.57 (115142 hom.)
• Consequence: SETD2 NM_014159.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.188

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-47017833-C-T is Benign according to our data. Variant chr3-47017833-C-T is described in ClinVar as [Benign]. Clinvar id is 1292763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD2	NM_014159.7	c.7432-94G>A		intron_variant		ENST00000409792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD2	ENST00000409792.4	c.7432-94G>A		intron_variant		5	NM_014159.7	P3

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83982 AN: 151832 Hom.: 23420 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.568 AC: 403109 AN: 709144 Hom.: 115142 AF XY: 0.567 AC XY: 213448 AN XY: 376488

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.542

Gnomad4 FIN exome AF: 0.606

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.553 AC: 84068 AN: 151952 Hom.: 23454 Cov.: 32 AF XY: 0.551 AC XY: 40932 AN XY: 74262

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.544

Alfa AF: 0.561 Hom.: 5346

Bravo AF: 0.545

Asia WGS AF: 0.611 AC: 2124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	2.7
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2385867; hg19: chr3-47059323; COSMIC: COSV57433232; COSMIC: COSV57433232;