6-45321795-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PVS1_Moderate BP6_Moderate

The ENST00000371460.5(SUPT3H):c.134+1G>T variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,599,428 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (4 hom.)
• Consequence: SUPT3H ENST00000371460.5 splice_donor
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0270

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 0 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.096251264 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BP6: Variant 6-45321795-C-A is Benign according to our data. Variant chr6-45321795-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 722245.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUPT3H	NM_003599.4	c.101+43406G>T		intron_variant		ENST00000371459.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUPT3H	ENST00000371460.5	c.134+1G>T		splice_donor_variant		1
SUPT3H	ENST00000371459.6	c.101+43406G>T		intron_variant		1	NM_003599.4	P1
SUPT3H	ENST00000475057.5	c.101+43406G>T		intron_variant, NMD_transcript_variant		2
SUPT3H	ENST00000459689.1	n.214+43406G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000761 AC: 184 AN: 241864 Hom.: 1 AF XY: 0.000704 AC XY: 92 AN XY: 130642

Gnomad AFR exome AF: 0.0000655

Gnomad AMR exome AF: 0.00239

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000461

Gnomad OTH exome AF: 0.00186

GnomAD4 exome AF: 0.000348 AC: 504 AN: 1447204 Hom.: 4 Cov.: 28 AF XY: 0.000378 AC XY: 272 AN XY: 719934

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00202

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00136

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000199

Gnomad4 OTH exome AF: 0.000552

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74418

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00165

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000245 Hom.: 0

Bravo AF: 0.000257

ExAC AF: 0.000643 AC: 78

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	19
Dann	Benign	0.83
Eigen	Benign	0.19
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.033	N
MutationTaster	Benign	1.0	N;N;N;N
GERP RS		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.67
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs188596507; hg19: chr6-45289532; COSMIC: COSV60947048;