chr6-44961776-C-A

Variant names:

• chr6-44961776-C-A
• NM_003599.4:c.557G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003599.4(SUPT3H):​c.557G>T​(p.Cys186Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,510 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SUPT3H NM_003599.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT3H	NM_003599.4	c.557G>T	p.Cys186Phe	missense_variant	Exon 7 of 11	ENST00000371459.6	NP_003590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUPT3H	ENST00000371459.6	c.557G>T	p.Cys186Phe	missense_variant	Exon 7 of 11	1	NM_003599.4	ENSP00000360514.1
SUPT3H	ENST00000371460.5	c.590G>T	p.Cys197Phe	missense_variant	Exon 9 of 13	1		ENSP00000360515.1
SUPT3H	ENST00000637763.2	c.371G>T	p.Cys124Phe	missense_variant	Exon 5 of 9	3		ENSP00000490652.2
SUPT3H	ENST00000475057.5	n.557G>T		non_coding_transcript_exon_variant	Exon 7 of 12	2		ENSP00000436411.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454510 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723436

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;.;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.73	T
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.9	D;D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.013	D;D;.
Sift4G	Uncertain	0.0070	D;D;.
Vest4		0.94
MVP		0.73
MPC		0.36
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.63

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: chr6-44929513;