Genetic Variant SUPT5H:p.Arg71Cys (chr19-39453491-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001111020.3(SUPT5H):c.211C>T(p.Arg71Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,395,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SUPT5H
NM_001111020.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Publications

0 publications found

Variant links:

Genes affected

SUPT5H (HGNC:11469): (SPT5 homolog, DSIF elongation factor subunit) Enables enzyme binding activity and protein heterodimerization activity. Involved in positive regulation of macroautophagy; regulation of RNA metabolic process; and transcription elongation from RNA polymerase II promoter. Located in nucleoplasm. Part of DSIF complex. [provided by Alliance of Genome Resources, Apr 2022]

SUPT5H links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2866447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111020.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUPT5H	NM_001111020.3	MANE Select	c.211C>T	p.Arg71Cys	missense	Exon 3 of 30	NP_001104490.1	O00267-1
SUPT5H	NM_001130824.2		c.211C>T	p.Arg71Cys	missense	Exon 3 of 30	NP_001124296.1	O00267-1
SUPT5H	NM_001319990.2		c.211C>T	p.Arg71Cys	missense	Exon 3 of 30	NP_001306919.1	O00267-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUPT5H	ENST00000432763.7	TSL:1 MANE Select	c.211C>T	p.Arg71Cys	missense	Exon 3 of 30	ENSP00000404029.4	O00267-1
SUPT5H	ENST00000598725.5	TSL:1	c.211C>T	p.Arg71Cys	missense	Exon 2 of 29	ENSP00000469090.1	O00267-1
SUPT5H	ENST00000359191.10	TSL:1	c.211C>T	p.Arg71Cys	missense	Exon 2 of 28	ENSP00000352117.6	O00267-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1395908

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

688636

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31418

American (AMR)

AF:

0.00

AC:

AN:

35326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24900

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

78822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00000279

AC:

AN:

1077048

Other (OTH)

AF:

0.00

AC:

AN:

57842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.0000111

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.78

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.022

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.1

PhyloP100

2.6

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.76

MutPred

0.20

Loss of solvent accessibility (P = 0.0329)

MVP

0.63

MPC

2.3

ClinPred

1.0

GERP RS

3.5

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.61

gMVP

0.12

Mutation Taster

=91/9

polymorphism

(source)

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