6-45127426-A-C

Position:

• chr6-45127426-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003599.4(SUPT3H):​c.102-21420T>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 151,940 control chromosomes in the GnomAD database, including 12,636 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 (12636 hom., cov: 32)
• Consequence: SUPT3H NM_003599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUPT3H	NM_003599.4	c.102-21420T>G		intron_variant		ENST00000371459.6	NP_003590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPT3H	ENST00000371459.6	c.102-21420T>G		intron_variant		1	NM_003599.4	ENSP00000360514	P1
SUPT3H	ENST00000371460.5	c.135-21420T>G		intron_variant		1		ENSP00000360515
SUPT3H	ENST00000475057.5	c.102-21420T>G		intron_variant, NMD_transcript_variant		2		ENSP00000436411

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60984 AN: 151822 Hom.: 12623 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.402 AC: 61023 AN: 151940 Hom.: 12636 Cov.: 32 AF XY: 0.403 AC XY: 29889 AN XY: 74248

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.429

Alfa AF: 0.409 Hom.: 27454

Bravo AF: 0.397

Asia WGS AF: 0.580 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs9395066; hg19: chr6-45095163;