3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Position:

• chr3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

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

The NM_014159.7(SETD2):​c.4918-43_4918-42insACACACAC 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 0.00075 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00042 (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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000748 (106/141664) while in subpopulation SAS AF= 0.00115 (5/4352). AF 95% confidence interval is 0.000525. There are 0 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD2	NM_014159.7	c.4918-43_4918-42insACACACAC		intron_variant		ENST00000409792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD2	ENST00000409792.4	c.4918-43_4918-42insACACACAC		intron_variant		5	NM_014159.7	P3

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 106 AN: 141566 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000741

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000568

Gnomad ASJ AF: 0.000298

Gnomad EAS AF: 0.000826

Gnomad SAS AF: 0.00115

Gnomad FIN AF: 0.00197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000420 AC: 249 AN: 592402 Hom.: 0 Cov.: 0 AF XY: 0.000428 AC XY: 135 AN XY: 315676

Gnomad4 AFR exome AF: 0.000549

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.0000626

Gnomad4 EAS exome AF: 0.00140

Gnomad4 SAS exome AF: 0.000664

Gnomad4 FIN exome AF: 0.000976

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.000306

GnomAD4 genome AF: 0.000748 AC: 106 AN: 141664 Hom.: 0 Cov.: 0 AF XY: 0.000728 AC XY: 50 AN XY: 68670

Gnomad4 AFR AF: 0.000739

Gnomad4 AMR AF: 0.000567

Gnomad4 ASJ AF: 0.000298

Gnomad4 EAS AF: 0.000828

Gnomad4 SAS AF: 0.00115

Gnomad4 FIN AF: 0.00197

Gnomad4 NFE AF: 0.000647

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;