Genetic Variant SUPT20HL1:p.Leu341Leu (chrX-24363781-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001136234.3(SUPT20HL1):c.1021T>C(p.Leu341Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 386,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 58 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.00037 ( 0 hom. 47 hem. )

Consequence

SUPT20HL1
NM_001136234.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0380

Variant links:

Genes affected

SUPT20HL1 (HGNC:30773): (SUPT20H like 1) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of SAGA complex. [provided by Alliance of Genome Resources, Apr 2022]

SUPT20HL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-24363781-T-C is Benign according to our data. Variant chrX-24363781-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660189.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.038 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT20HL1	NM_001136234.3 link	c.1021T>C	p.Leu341Leu	synonymous_variant	Exon 1 of 1	ENST00000686983.1	NP_001129706.3	A0A7I2YQ69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUPT20HL1	ENST00000686983.1 link	c.1021T>C	p.Leu341Leu	synonymous_variant	Exon 1 of 1		NM_001136234.3	ENSP00000509731.1		A0A7I2YQ69
SUPT20HL1	ENST00000436466.2 link	c.1021T>C	p.Leu341Leu	synonymous_variant	Exon 2 of 2	6		ENSP00000502907.1		A0A7I2YQ69

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

111795

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

33987

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00591

Gnomad SAS

AF:

0.000389

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.000469

AC:

AN:

181216

Hom.:

AF XY:

0.000488

AC XY:

AN XY:

67568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00480

Gnomad SAS exome

AF:

0.000368

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000448

GnomAD4 exome

AF:

0.000372

AC:

102

AN:

274332

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

108938

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00622

Gnomad4 SAS exome

AF:

0.000476

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.000403

GnomAD4 genome

AF:

0.000277

AC:

AN:

111849

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

34051

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00593

Gnomad4 SAS

AF:

0.000390

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000656

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUPT20HL1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.30

DANN

Benign

0.45

Splicing

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