3-47101501-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014159.7(SETD2):​c.4972T>A​(p.Ser1658Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

SETD2
NM_014159.7 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.74
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SETD2NM_014159.7 linkc.4972T>A p.Ser1658Thr missense_variant 8/21 ENST00000409792.4 NP_054878.5 Q9BYW2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SETD2ENST00000409792.4 linkc.4972T>A p.Ser1658Thr missense_variant 8/215 NM_014159.7 ENSP00000386759.3 Q9BYW2-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.51
D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Benign
0.38
N;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.3
N;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0060
D;.
Sift4G
Uncertain
0.024
D;.
Polyphen
0.75
P;.
Vest4
0.36
MutPred
0.38
Gain of glycosylation at T1663 (P = 0.0351);.;
MVP
0.83
MPC
2.0
ClinPred
0.88
D
GERP RS
5.9
Varity_R
0.33
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: chr3-47142991; API