13-37017252-C-T

Position:

• chr13-37017252-C-T

Variant summary

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

The NM_001014286.3(SUPT20H):​c.1985G>A​(p.Gly662Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: SUPT20H NM_001014286.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66

Genes affected

SUPT20H (HGNC:20596): (SPT20 homolog, SAGA complex component) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of gluconeogenesis and positive regulation of transcription by RNA polymerase II. Part of SAGA-type complex. [provided by Alliance of Genome Resources, Apr 2022]

SUPT20H (HGNC:):

EXOSC8 (HGNC:17035): (exosome component 8) This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

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=0.10281789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUPT20H	NM_001014286.3	c.1985G>A	p.Gly662Glu	missense_variant	23/26	ENST00000350612.11	NP_001014308.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPT20H	ENST00000350612.11	c.1985G>A	p.Gly662Glu	missense_variant	23/26	1	NM_001014286.3	ENSP00000218894.10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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 24, 2024

The c.1985G>A (p.G662E) alteration is located in exon 23 (coding exon 22) of the SUPT20H gene. This alteration results from a G to A substitution at nucleotide position 1985, causing the glycine (G) at amino acid position 662 to be replaced by a glutamic acid (E). 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	0.083
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	.;.;.;T;.;.
Eigen	Benign	-0.037
Eigen_PC	Benign	0.0077
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	.;D;.;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;.;.;L;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N;N;N;N;.;N
REVEL	Benign	0.063
Sift	Benign	0.38	T;T;T;T;.;T
Sift4G	Benign	0.27	T;T;T;T;T;T
Polyphen		0.0020	B;.;B;B;.;B
Vest4		0.31
MutPred		0.19		.;.;.;Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);.;
MVP		0.29
MPC		0.36
ClinPred		0.52	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs2060667825; hg19: chr13-37591389;