Genetic Variant NM_003168.3:c.243G>C (chr17-58347231-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SUPT4H1
NM_003168.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Publications

0 publications found

Variant links:

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]

SUPT4H1 links:

ENSG00000285897 (HGNC:):

ENSG00000285897 links:

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

TSPOAP1-AS1 links:

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ACMG classification

Classification was made for transcript

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251410

AF XY:

0.00000736

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Benign

-0.026

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0045

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.4

PhyloP100

2.9

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Benign

0.44

Sift4G

Benign

0.47

Polyphen

0.0050

Vest4

0.79

MutPred

0.52

Loss of methylation at K81 (P = 0.0145)

MVP

0.26

MPC

0.88

ClinPred

0.35

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over