chr6-45003751-T-C

Variant names:

• chr6-45003751-T-C
• NM_003599.4:c.406A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003599.4(SUPT3H):​c.406A>G​(p.Ile136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SUPT3H NM_003599.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074000716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT3H	NM_003599.4	c.406A>G	p.Ile136Val	missense_variant	Exon 6 of 11	ENST00000371459.6	NP_003590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUPT3H	ENST00000371459.6	c.406A>G	p.Ile136Val	missense_variant	Exon 6 of 11	1	NM_003599.4	ENSP00000360514.1
SUPT3H	ENST00000371460.5	c.439A>G	p.Ile147Val	missense_variant	Exon 8 of 13	1		ENSP00000360515.1
SUPT3H	ENST00000637763.2	c.220A>G	p.Ile74Val	missense_variant	Exon 4 of 9	3		ENSP00000490652.2
SUPT3H	ENST00000475057.5	n.406A>G		non_coding_transcript_exon_variant	Exon 6 of 12	2		ENSP00000436411.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461498 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.77
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.011
Sift	Benign	0.52	T;T
Sift4G	Benign	0.29	T;T
Vest4		0.26
MVP		0.17
MPC		0.044
ClinPred		0.14	T
GERP RS		0.19
Varity_R		0.029
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-44971488;