6-45020556-C-A

Variant names:

• chr6-45020556-C-A
• rs150635035
• NM_003599.4:c.263G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003599.4(SUPT3H):​c.263G>T​(p.Arg88Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,457,848 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SUPT3H NM_003599.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003599.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT3H	NM_003599.4	MANE Select	c.263G>T	p.Arg88Leu	missense	Exon 4 of 11	NP_003590.1	O75486-1
	SUPT3H	NM_181356.3		c.296G>T	p.Arg99Leu	missense	Exon 6 of 13	NP_852001.1	O75486-4
	SUPT3H	NM_001350324.2		c.263G>T	p.Arg88Leu	missense	Exon 4 of 12	NP_001337253.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT3H	ENST00000371459.6	TSL:1 MANE Select	c.263G>T	p.Arg88Leu	missense	Exon 4 of 11	ENSP00000360514.1	O75486-1
	SUPT3H	ENST00000371460.5	TSL:1	c.296G>T	p.Arg99Leu	missense	Exon 6 of 13	ENSP00000360515.1	O75486-4
	SUPT3H	ENST00000889037.1		c.317G>T	p.Arg106Leu	missense	Exon 5 of 12	ENSP00000559096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457848 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725204

African (AFR) AF: 0.0000300 AC: 1 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 85780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109346

Other (OTH) AF: 0.0000166 AC: 1 AN: 60214

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.25	D
PhyloP100		5.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Vest4		0.95
MVP		0.97
MPC		0.35
ClinPred		0.99	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.85
Mutation Taster		=14/86	disease causing

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

Other links and lift over

dbSNP: rs150635035; hg19: chr6-44988293;