Variant 19-39465056-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001111020.3(SUPT5H):c.876+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,607,882 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 32 hom. )

Consequence

SUPT5H
NM_001111020.3 splice_region, intron

Scores

Splicing: ADA: 0.0005190

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.517

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 19-39465056-G-A is Benign according to our data. Variant chr19-39465056-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649835.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-39465056-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 497 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUPT5H	NM_001111020.3 linkuse as main transcript	c.876+7G>A		splice_region_variant, intron_variant		ENST00000432763.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUPT5H	ENST00000432763.7 linkuse as main transcript	c.876+7G>A		splice_region_variant, intron_variant		1	NM_001111020.3	P1	O00267-1

Frequencies

GnomAD3 genomes

AF:

0.00327

AC:

497

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00561

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00407

AC:

1009

AN:

247714

Hom.:

AF XY:

0.00400

AC XY:

536

AN XY:

133960

show subpopulations

Gnomad AFR exome

AF:

0.000621

Gnomad AMR exome

AF:

0.00198

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00496

Gnomad NFE exome

AF:

0.00716

Gnomad OTH exome

AF:

0.00416

GnomAD4 exome

AF:

0.00568

AC:

8261

AN:

1455544

Hom.:

Cov.:

AF XY:

0.00547

AC XY:

3952

AN XY:

722938

show subpopulations

Gnomad4 AFR exome

AF:

0.000868

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.0000774

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00451

Gnomad4 NFE exome

AF:

0.00693

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00326

AC:

497

AN:

152338

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

215

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00561

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00481

Hom.:

Bravo

AF:

0.00345

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

SUPT5H: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.1

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.028

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

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