chr17-58347231-C-A

Variant names:

• chr17-58347231-C-A
• rs763950244
• NM_003168.3:c.243G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict a benign outcome for this variant. 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003168.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT4H1	NM_003168.3	MANE Select	c.243G>T	p.Lys81Asn	missense	Exon 4 of 5	NP_003159.1	P63272
	SUPT4H1	NR_073470.2		n.311G>T		non_coding_transcript_exon	Exon 4 of 5
	TSPOAP1-AS1	NR_038410.1		n.584-4513C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT4H1	ENST00000225504.8	TSL:1 MANE Select	c.243G>T	p.Lys81Asn	missense	Exon 4 of 5	ENSP00000225504.3	P63272
	ENSG00000285897	ENST00000648873.1		n.*334G>T		non_coding_transcript_exon	Exon 12 of 13	ENSP00000497686.1	A0A3B3ITA1
	ENSG00000285897	ENST00000648873.1		n.*334G>T		3_prime_UTR	Exon 12 of 13	ENSP00000497686.1	A0A3B3ITA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.026
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.9
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.44	T
Sift4G	Benign	0.47	T
Polyphen		0.0050	B
Vest4		0.79
MutPred		0.52		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

Other links and lift over

dbSNP: rs763950244; hg19: chr17-56424592;