17-58347231-C-G

Variant names:

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

Variant summary

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

The NM_003168.3(SUPT4H1):​c.243G>C​(p.Lys81Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUPT4H1 NM_003168.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 rank	MANE	Protein	UniProt
SUPT4H1	NM_003168.3	c.243G>C	p.Lys81Asn	missense_variant	Exon 4 of 5	ENST00000225504.8	NP_003159.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251410 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.14	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	0.49	T;T;T;T
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		0.35	T
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;