chr6-45020565-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003599.4(SUPT3H):c.254T>C(p.Phe85Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,611,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SUPT3H
NM_003599.4 missense
NM_003599.4 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 6.42
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.906
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUPT3H | NM_003599.4 | c.254T>C | p.Phe85Ser | missense_variant | 4/11 | ENST00000371459.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUPT3H | ENST00000371459.6 | c.254T>C | p.Phe85Ser | missense_variant | 4/11 | 1 | NM_003599.4 | P1 | |
SUPT3H | ENST00000371460.5 | c.287T>C | p.Phe96Ser | missense_variant | 6/13 | 1 | |||
SUPT3H | ENST00000637763.2 | c.68T>C | p.Phe23Ser | missense_variant | 2/9 | 3 | |||
SUPT3H | ENST00000475057.5 | c.254T>C | p.Phe85Ser | missense_variant, NMD_transcript_variant | 4/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250204Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135302
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459408Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15AN XY: 726000
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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 submitter | clinical testing | Ambry Genetics | Nov 17, 2022 | The c.287T>C (p.F96S) alteration is located in exon 6 (coding exon 4) of the SUPT3H gene. This alteration results from a T to C substitution at nucleotide position 287, causing the phenylalanine (F) at amino acid position 96 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at