rs756574775

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003599.4(SUPT3H):​c.557G>T​(p.Cys186Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SUPT3H
NM_003599.4 missense

Scores

8
6
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.29
Variant links:
Genes affected
SUPT3H (HGNC:11466): (SPT3 homolog, SAGA and STAGA complex component) Enables transcription coactivator activity. Involved in histone H3 acetylation and histone deubiquitination. Located in nucleoplasm. Part of SAGA complex and transcription factor TFTC complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUPT3HNM_003599.4 linkc.557G>T p.Cys186Phe missense_variant Exon 7 of 11 ENST00000371459.6 NP_003590.1 O75486-1A0A024RD67

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUPT3HENST00000371459.6 linkc.557G>T p.Cys186Phe missense_variant Exon 7 of 11 1 NM_003599.4 ENSP00000360514.1 O75486-1
SUPT3HENST00000371460.5 linkc.590G>T p.Cys197Phe missense_variant Exon 9 of 13 1 ENSP00000360515.1 O75486-4
SUPT3HENST00000637763.2 linkc.371G>T p.Cys124Phe missense_variant Exon 5 of 9 3 ENSP00000490652.2 A0A1B0GVT7
SUPT3HENST00000475057.5 linkn.557G>T non_coding_transcript_exon_variant Exon 7 of 12 2 ENSP00000436411.1 O75486-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1454510
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
723436
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
.;.;T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Pathogenic
0.83
D;D;D
MetaSVM
Benign
-0.73
T
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-5.9
D;D;.
REVEL
Uncertain
0.43
Sift
Uncertain
0.013
D;D;.
Sift4G
Uncertain
0.0070
D;D;.
Vest4
0.94
MVP
0.73
MPC
0.36
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.80
gMVP
0.63

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: chr6-44929513; API