6-44961826-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003599.4(SUPT3H):​c.507A>C​(p.Arg169Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SUPT3H
NM_003599.4 missense, splice_region

Scores

4
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUPT3HNM_003599.4 linkc.507A>C p.Arg169Ser missense_variant, splice_region_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.507A>C p.Arg169Ser missense_variant, splice_region_variant Exon 7 of 11 1 NM_003599.4 ENSP00000360514.1 O75486-1
SUPT3HENST00000371460.5 linkc.540A>C p.Arg180Ser missense_variant, splice_region_variant Exon 9 of 13 1 ENSP00000360515.1 O75486-4
SUPT3HENST00000637763.2 linkc.321A>C p.Arg107Ser missense_variant, splice_region_variant Exon 5 of 9 3 ENSP00000490652.2 A0A1B0GVT7
SUPT3HENST00000475057.5 linkn.507A>C splice_region_variant, non_coding_transcript_exon_variant Exon 7 of 12 2 ENSP00000436411.1 O75486-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
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
Oct 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.540A>C (p.R180S) alteration is located in exon 9 (coding exon 7) of the SUPT3H gene. This alteration results from a A to C substitution at nucleotide position 540, causing the arginine (R) at amino acid position 180 to be replaced by a serine (S). 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
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
.;.;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.076
D
MetaRNN
Uncertain
0.70
D;D;D
MetaSVM
Benign
-0.74
T
PrimateAI
Uncertain
0.63
T
PROVEAN
Pathogenic
-5.4
D;D;.
REVEL
Uncertain
0.37
Sift
Uncertain
0.0030
D;D;.
Sift4G
Uncertain
0.0030
D;D;.
Vest4
0.95
MVP
0.58
MPC
0.34
ClinPred
1.0
D
GERP RS
3.3
Varity_R
0.93
gMVP
0.71

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: chr6-44929563; API