6-44954539-C-G

Variant names:

• chr6-44954539-C-G
• rs748728560
• NM_003599.4:c.649G>C

Variant summary

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

The NM_003599.4(SUPT3H):​c.649G>C​(p.Ala217Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,040 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SUPT3H NM_003599.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT3H	NM_003599.4	c.649G>C	p.Ala217Pro	missense_variant	Exon 8 of 11	ENST00000371459.6	NP_003590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUPT3H	ENST00000371459.6	c.649G>C	p.Ala217Pro	missense_variant	Exon 8 of 11	1	NM_003599.4	ENSP00000360514.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152040 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74272

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.73	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.0	D;D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D;D;.
Sift4G	Benign	0.088	T;T;.
Vest4		0.93
MVP		0.70
MPC		0.35
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.85
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748728560; hg19: chr6-44922276;