rs2064294530

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017438.5(SETD4):​c.559G>T​(p.Ala187Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A187P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SETD4
NM_017438.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100
Variant links:
Genes affected
SETD4 (HGNC:1258): (SET domain containing 4) Enables histone methyltransferase activity (H4-K20 specific). Involved in histone H4-K20 trimethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.040385514).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETD4NM_017438.5 linkc.559G>T p.Ala187Ser missense_variant Exon 6 of 12 ENST00000332131.9 NP_059134.1 Q9NVD3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SETD4ENST00000332131.9 linkc.559G>T p.Ala187Ser missense_variant Exon 6 of 12 2 NM_017438.5 ENSP00000329189.4 Q9NVD3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
12
DANN
Benign
0.77
DEOGEN2
Benign
0.011
T;.;T;.;.;.;.;.;.
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.75
.;T;T;.;.;T;T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.040
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.7
L;.;L;.;L;.;L;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
0.64
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.082
Sift
Benign
1.0
T;T;T;T;T;T;T;T;T
Sift4G
Benign
1.0
T;.;T;.;T;.;T;.;.
Polyphen
0.0090
B;B;B;B;.;B;.;B;.
Vest4
0.21
MutPred
0.35
Gain of helix (P = 0.062);.;Gain of helix (P = 0.062);.;Gain of helix (P = 0.062);.;Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP
0.31
MPC
0.17
ClinPred
0.16
T
GERP RS
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.054
gMVP
0.31

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: chr21-37418047; API