6-45276678-T-C

Variant names:

• chr6-45276678-T-C
• rs10948222
• NM_003599.4:c.101+88523A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003599.4(SUPT3H):​c.101+88523A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,098 control chromosomes in the GnomAD database, including 12,704 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12704 hom., cov: 32)
• Consequence: SUPT3H NM_003599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT3H	NM_003599.4	c.101+88523A>G		intron_variant	Intron 2 of 10	ENST00000371459.6	NP_003590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUPT3H	ENST00000371459.6	c.101+88523A>G		intron_variant	Intron 2 of 10	1	NM_003599.4	ENSP00000360514.1
SUPT3H	ENST00000371460.5	c.134+45118A>G		intron_variant	Intron 4 of 12	1		ENSP00000360515.1
SUPT3H	ENST00000459689.1	n.215-25542A>G		intron_variant	Intron 2 of 2	2
SUPT3H	ENST00000475057.5	n.101+88523A>G		intron_variant	Intron 2 of 11	2		ENSP00000436411.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61071 AN: 151980 Hom.: 12689 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61109 AN: 152098 Hom.: 12704 Cov.: 32 AF XY: 0.403 AC XY: 29935 AN XY: 74356

African (AFR) AF: 0.337 AC: 13988 AN: 41490

American (AMR) AF: 0.373 AC: 5705 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3664 AN: 5172

South Asian (SAS) AF: 0.494 AC: 2383 AN: 4828

European-Finnish (FIN) AF: 0.416 AC: 4403 AN: 10584

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27831 AN: 67962

Other (OTH) AF: 0.425 AC: 894 AN: 2106

Alfa AF: 0.412 Hom.: 24519

Bravo AF: 0.396

Asia WGS AF: 0.577 AC: 2005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.77
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs10948222; hg19: chr6-45244415;