6-44961815-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003599.4(SUPT3H):ā€‹c.518A>Gā€‹(p.Gln173Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,607,598 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SUPT3H
NM_003599.4 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32985884).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUPT3HNM_003599.4 linkc.518A>G p.Gln173Arg 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.518A>G p.Gln173Arg missense_variant Exon 7 of 11 1 NM_003599.4 ENSP00000360514.1 O75486-1
SUPT3HENST00000371460.5 linkc.551A>G p.Gln184Arg missense_variant Exon 9 of 13 1 ENSP00000360515.1 O75486-4
SUPT3HENST00000637763.2 linkc.332A>G p.Gln111Arg missense_variant Exon 5 of 9 3 ENSP00000490652.2 A0A1B0GVT7
SUPT3HENST00000475057.5 linkn.518A>G non_coding_transcript_exon_variant Exon 7 of 12 2 ENSP00000436411.1 O75486-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455368
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
723652
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000624
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.551A>G (p.Q184R) alteration is located in exon 9 (coding exon 7) of the SUPT3H gene. This alteration results from a A to G substitution at nucleotide position 551, causing the glutamine (Q) at amino acid position 184 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
0.21
BayesDel_addAF
Benign
-0.028
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
.;.;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-2.1
N;N;.
REVEL
Benign
0.13
Sift
Benign
0.36
T;T;.
Sift4G
Benign
0.35
T;T;.
Vest4
0.60
MVP
0.26
MPC
0.21
ClinPred
0.86
D
GERP RS
5.7
Varity_R
0.21
gMVP
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1374582893; hg19: chr6-44929552; API