3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Position:

• chr3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014159.7(SETD2):​c.4918-54_4918-43dupACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SETD2 NM_014159.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000113 (16/141572) while in subpopulation AMR AF= 0.000568 (8/14082). AF 95% confidence interval is 0.000282. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD2	NM_014159.7	c.4918-54_4918-43dupACACACACACAC		intron_variant		ENST00000409792.4	NP_054878.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD2	ENST00000409792.4	c.4918-54_4918-43dupACACACACACAC		intron_variant		5	NM_014159.7	ENSP00000386759.3

Frequencies

GnomAD3 genomes AF: 0.000113 AC: 16 AN: 141572 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000568

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000135 AC: 8 AN: 592440 Hom.: 0 Cov.: 0 AF XY: 0.00000950 AC XY: 3 AN XY: 315702

Gnomad4 AFR exome AF: 0.0000686

Gnomad4 AMR exome AF: 0.0000336

Gnomad4 ASJ exome AF: 0.0000626

Gnomad4 EAS exome AF: 0.0000317

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000538

Gnomad4 OTH exome AF: 0.0000679

GnomAD4 genome AF: 0.000113 AC: 16 AN: 141572 Hom.: 0 Cov.: 0 AF XY: 0.000117 AC XY: 8 AN XY: 68566

Gnomad4 AFR AF: 0.000212

Gnomad4 AMR AF: 0.000568

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61571386; hg19: chr3-47143087;