chr6-44999753-T-C

Variant names:

• chr6-44999753-T-C
• rs10948197
• NM_003599.4:c.504+3900A>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.504+3900A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,904 control chromosomes in the GnomAD database, including 9,862 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 0.35 (9862 hom., cov: 32)
• Consequence: SUPT3H NM_003599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 21 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT3H	NM_003599.4	c.504+3900A>G		intron_variant	Intron 6 of 10	ENST00000371459.6	NP_003590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUPT3H	ENST00000371459.6	c.504+3900A>G		intron_variant	Intron 6 of 10	1	NM_003599.4	ENSP00000360514.1
SUPT3H	ENST00000371460.5	c.537+3900A>G		intron_variant	Intron 8 of 12	1		ENSP00000360515.1
SUPT3H	ENST00000637763.2	c.318+3900A>G		intron_variant	Intron 4 of 8	3		ENSP00000490652.2
SUPT3H	ENST00000475057.5	n.504+3900A>G		intron_variant	Intron 6 of 11	2		ENSP00000436411.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53010 AN: 151786 Hom.: 9849 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.349 AC: 53053 AN: 151904 Hom.: 9862 Cov.: 32 AF XY: 0.351 AC XY: 26084 AN XY: 74218

African (AFR) AF: 0.211 AC: 8767 AN: 41506

American (AMR) AF: 0.416 AC: 6321 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1536 AN: 5156

South Asian (SAS) AF: 0.313 AC: 1510 AN: 4818

European-Finnish (FIN) AF: 0.413 AC: 4365 AN: 10560

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 28000 AN: 67900

Other (OTH) AF: 0.361 AC: 760 AN: 2104

Alfa AF: 0.393 Hom.: 23678

Bravo AF: 0.347

Asia WGS AF: 0.283 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-0.37
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: rs10948197; hg19: chr6-44967490;