Variant chr19-39469288-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001111020.3(SUPT5H):c.1264C>T(p.Pro422Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P422L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SUPT5H
NM_001111020.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22939718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUPT5H	NM_001111020.3 linkuse as main transcript	c.1264C>T	p.Pro422Ser	missense_variant	16/30	ENST00000432763.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUPT5H	ENST00000432763.7 linkuse as main transcript	c.1264C>T	p.Pro422Ser	missense_variant	16/30	1	NM_001111020.3	P1	O00267-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250758

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

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

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.1264C>T (p.P422S) alteration is located in exon 15 (coding exon 15) of the SUPT5H gene. This alteration results from a C to T substitution at nucleotide position 1264, causing the proline (P) at amino acid position 422 to be replaced by a serine (S). 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

Benign

0.24

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;.;.;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.92

.;D;D;.;.

M_CAP

Benign

0.0098

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.69

N;N;.;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.2

.;D;D;.;.

REVEL

Benign

0.13

Sift

Benign

0.34

.;T;T;.;.

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.019

B;B;B;B;B

Vest4

0.25

MutPred

0.37

Gain of glycosylation at P422 (P = 0.0098);Gain of glycosylation at P422 (P = 0.0098);.;.;Gain of glycosylation at P422 (P = 0.0098);

MVP

0.42

MPC

0.96

ClinPred

0.42

GERP RS

5.8

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Varity_R

0.43

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over