chr6-45105960-A-C

Position:

• chr6-45105960-A-C

Variant summary

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

The NM_003599.4(SUPT3H):​c.148T>G​(p.Leu50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUPT3H NM_003599.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

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/exons	MANE	Protein	UniProt
SUPT3H	NM_003599.4	c.148T>G	p.Leu50Val	missense_variant	3/11	ENST00000371459.6	NP_003590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPT3H	ENST00000371459.6	c.148T>G	p.Leu50Val	missense_variant	3/11	1	NM_003599.4	ENSP00000360514	P1
SUPT3H	ENST00000371460.5	c.181T>G	p.Leu61Val	missense_variant	5/13	1		ENSP00000360515
SUPT3H	ENST00000637763.2	c.-39T>G		5_prime_UTR_variant	1/9	3		ENSP00000490652
SUPT3H	ENST00000475057.5	c.148T>G	p.Leu50Val	missense_variant, NMD_transcript_variant	3/12	2		ENSP00000436411

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

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

Nov 21, 2022

The c.181T>G (p.L61V) alteration is located in exon 5 (coding exon 3) of the SUPT3H gene. This alteration results from a T to G substitution at nucleotide position 181, causing the leucine (L) at amino acid position 61 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.027	D;D
Vest4		0.56
MVP		0.61
MPC		0.31
ClinPred		0.93	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.52

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: rs1799212695; hg19: chr6-45073697;