3-47124012-T-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_014159.7(SETD2):​c.624A>T​(p.Val208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V208V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SETD2
NM_014159.7 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.158
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP7
Synonymous conserved (PhyloP=0.158 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SETD2NM_014159.7 linkuse as main transcriptc.624A>T p.Val208= synonymous_variant 3/21 ENST00000409792.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SETD2ENST00000409792.4 linkuse as main transcriptc.624A>T p.Val208= synonymous_variant 3/215 NM_014159.7 P3Q9BYW2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
5.8
DANN
Benign
0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-47165502; API