chr17-58347231-C-A

Position:

• chr17-58347231-C-A

Variant summary

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

The NM_003168.3(SUPT4H1):​c.243G>T​(p.Lys81Asn) 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: SUPT4H1 NM_003168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90

Genes affected

SUPT4H1 (HGNC:11467): (SPT4 homolog, DSIF elongation factor subunit) This gene encodes the small subunit of DRB (5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF) complex, which regulates mRNA processing and transcription elongation by RNA polymerase II. The encoded protein is localized to the nucleus and interacts with the large subunit (SUPT5H) to form the DSIF complex. Related pseudogenes have been identified on chromosomes 2 and 12. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2012]

ENSG00000285897 (HGNC:):

TSPOAP1-AS1 (HGNC:44148): (TSPOAP1, SUPT4H1 and RNF43 antisense RNA 1)

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
SUPT4H1	NM_003168.3	c.243G>T	p.Lys81Asn	missense_variant	4/5	ENST00000225504.8	NP_003159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPT4H1	ENST00000225504.8	c.243G>T	p.Lys81Asn	missense_variant	4/5	1	NM_003168.3	ENSP00000225504.3
ENSG00000285897	ENST00000648873.1	n.*334G>T		non_coding_transcript_exon_variant	12/13			ENSP00000497686.1
ENSG00000285897	ENST00000648873.1	n.*334G>T		3_prime_UTR_variant	12/13			ENSP00000497686.1

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

Apr 04, 2023

The c.243G>T (p.K81N) alteration is located in exon 4 (coding exon 4) of the SUPT4H1 gene. This alteration results from a G to T substitution at nucleotide position 243, causing the lysine (K) at amino acid position 81 to be replaced by an asparagine (N). 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	0.89
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T;.;.;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L;.;.;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.44	T;.;.;.
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.0050	B;.;.;B
Vest4		0.79
MutPred		0.52		Loss of methylation at K81 (P = 0.0145);.;.;Loss of methylation at K81 (P = 0.0145);
MVP		0.26
MPC		0.88
ClinPred		0.75	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.78

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: rs763950244; hg19: chr17-56424592;