17-28678621-A-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003170.5(SUPT6H):c.1193A>T(p.Gln398Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
SUPT6H
NM_003170.5 missense
NM_003170.5 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 8.77
Genes affected
SUPT6H (HGNC:11470): (SPT6 homolog, histone chaperone and transcription elongation factor) Enables histone binding activity. Involved in negative regulation of histone H3-K27 methylation and positive regulation of transcription elongation from RNA polymerase II promoter. Predicted to be located in nucleoplasm. Predicted to be part of transcription elongation factor complex. Predicted to be active in transcriptionally active chromatin. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.24807829).
BS2
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUPT6H | NM_003170.5 | c.1193A>T | p.Gln398Leu | missense_variant | 10/37 | ENST00000314616.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUPT6H | ENST00000314616.11 | c.1193A>T | p.Gln398Leu | missense_variant | 10/37 | 1 | NM_003170.5 | P1 | |
SUPT6H | ENST00000347486.8 | c.1193A>T | p.Gln398Leu | missense_variant | 11/38 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000215 AC: 54AN: 251450Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135900
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GnomAD4 exome AF: 0.0000540 AC: 79AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727228
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GnomAD4 genome AF: 0.0000919 AC: 14AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74498
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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 | Apr 13, 2022 | The c.1193A>T (p.Q398L) alteration is located in exon 10 (coding exon 9) of the SUPT6H gene. This alteration results from a A to T substitution at nucleotide position 1193, causing the glutamine (Q) at amino acid position 398 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Loss of solvent accessibility (P = 0.0635);Loss of solvent accessibility (P = 0.0635);
MVP
MPC
ClinPred
T
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