3-4303393-C-G

Variant summary

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

The NM_006515.4(SETMAR):​c.23C>G​(p.Thr8Arg) variant causes a missense 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SETMAR
NM_006515.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.462
Variant links:
Genes affected
SETMAR (HGNC:10762): (SET domain and mariner transposase fusion gene) This gene encodes a fusion protein that contains an N-terminal histone-lysine N-methyltransferase domain and a C-terminal mariner transposase domain. The encoded protein binds DNA and functions in DNA repair activities including non-homologous end joining and double strand break repair. The SET domain portion of this protein specifically methylates histone H3 lysines 4 and 36. This gene exists as a fusion gene only in anthropoid primates, other organisms lack mariner transposase domain. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

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=0.05201575).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SETMARNM_006515.4 linkc.23C>G p.Thr8Arg missense_variant 1/3 ENST00000358065.5 NP_006506.3 Q53H47-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SETMARENST00000358065.5 linkc.23C>G p.Thr8Arg missense_variant 1/31 NM_006515.4 ENSP00000373354.3 Q53H47-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 03, 2023The c.23C>G (p.T8R) alteration is located in exon 1 (coding exon 1) of the SETMAR gene. This alteration results from a C to G substitution at nucleotide position 23, causing the threonine (T) at amino acid position 8 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
0.44
DANN
Benign
0.80
DEOGEN2
Benign
0.0050
T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.45
T;T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.052
T;T;T
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Benign
-0.69
N;N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
0.23
N;N;N
REVEL
Benign
0.12
Sift
Benign
0.15
T;T;T
Sift4G
Benign
0.34
T;T;T
Vest4
0.049
MutPred
0.23
Gain of MoRF binding (P = 0.0048);Gain of MoRF binding (P = 0.0048);Gain of MoRF binding (P = 0.0048);
MVP
0.58
MPC
0.029
ClinPred
0.080
T
GERP RS
-4.6
Varity_R
0.061
gMVP
0.073

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr3-4345077; API