chr6-45014830-T-C

Position:

• chr6-45014830-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_003599.4(SUPT3H):​c.335A>G​(p.Lys112Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,440,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SUPT3H NM_003599.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

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 4 ACMG points.

• PM1: In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity SUPT3_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUPT3H	NM_003599.4	c.335A>G	p.Lys112Arg	missense_variant	5/11	ENST00000371459.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUPT3H	ENST00000371459.6	c.335A>G	p.Lys112Arg	missense_variant	5/11	1	NM_003599.4	P1
SUPT3H	ENST00000371460.5	c.368A>G	p.Lys123Arg	missense_variant	7/13	1
SUPT3H	ENST00000637763.2	c.149A>G	p.Lys50Arg	missense_variant	3/9	3
SUPT3H	ENST00000475057.5	c.335A>G	p.Lys112Arg	missense_variant, NMD_transcript_variant	5/12	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1440940 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 716320

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000241

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: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.368A>G (p.K123R) alteration is located in exon 7 (coding exon 5) of the SUPT3H gene. This alteration results from a A to G substitution at nucleotide position 368, causing the lysine (K) at amino acid position 123 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.17
Sift	Benign	0.13	T;T
Sift4G	Benign	0.15	T;T
Vest4		0.59
MVP		0.58
MPC		0.076
ClinPred		0.88	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-44982567;