chr17-28674546-A-T

Position:

• chr17-28674546-A-T

Variant summary

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

The NM_003170.5(SUPT6H):​c.278A>T​(p.Asp93Val) variant causes a missense change. 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: SUPT6H NM_003170.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

Genes affected

SUPT6H (HGNC:11470): (SPT6 homolog, histone chaperone and transcription elongation factor) Enables histone binding activity. Involved in negative regulation of histone H3-K27 methylation and positive regulation of transcription elongation from RNA polymerase II promoter. Predicted to be located in nucleoplasm. Predicted to be part of transcription elongation factor complex. Predicted to be active in transcriptionally active chromatin. [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	UniProt
SUPT6H	NM_003170.5	c.278A>T	p.Asp93Val	missense_variant	4/37	ENST00000314616.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUPT6H	ENST00000314616.11	c.278A>T	p.Asp93Val	missense_variant	4/37	1	NM_003170.5	P1
SUPT6H	ENST00000347486.8	c.278A>T	p.Asp93Val	missense_variant	5/38	1		P1
SUPT6H	ENST00000584312.1	c.*224A>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 08, 2024

The c.278A>T (p.D93V) alteration is located in exon 4 (coding exon 3) of the SUPT6H gene. This alteration results from a A to T substitution at nucleotide position 278, causing the aspartic acid (D) at amino acid position 93 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.9	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.92	P;P
Vest4		0.70
MutPred		0.43		Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.44
MPC		0.89
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.76
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2030622913; hg19: chr17-27001564;