Genetic Variant SUPT20HL1:p.Ala514_Ala517del (chrX-24364256-TTGCTGCTGCTGC-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BS1_SupportingBS2

The NM_001136234.3(SUPT20HL1):c.1540_1551delGCTGCTGCTGCT(p.Ala514_Ala517del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 802,774 control chromosomes in the GnomAD database, including 12 homozygotes. There are 599 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0046 ( 1 hom., 100 hem., cov: 2)

Exomes 𝑓: 0.0021 ( 11 hom. 499 hem. )

Consequence

SUPT20HL1
NM_001136234.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 0.439

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001136234.3

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00458 (376/82128) while in subpopulation SAS AF= 0.0233 (32/1371). AF 95% confidence interval is 0.017. There are 1 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Hemizygotes in GnomAd4 at 100 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT20HL1	NM_001136234.3 link	c.1540_1551delGCTGCTGCTGCT	p.Ala514_Ala517del	conservative_inframe_deletion	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.1540_1551delGCTGCTGCTGCT	p.Ala514_Ala517del	conservative_inframe_deletion	Exon 1 of 1		NM_001136234.3	ENSP00000509731.1		A0A7I2YQ69
SUPT20HL1	ENST00000436466.2 link	c.1540_1551delGCTGCTGCTGCT	p.Ala514_Ala517del	conservative_inframe_deletion	Exon 2 of 2	6		ENSP00000502907.1		A0A7I2YQ69

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

377

AN:

82121

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

101

AN XY:

19273

show subpopulations

Gnomad AFR

AF:

0.00999

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00345

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00286

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00177

Gnomad OTH

AF:

0.00562

GnomAD4 exome

AF:

0.00206

AC:

1486

AN:

720646

Hom.:

AF XY:

0.00222

AC XY:

499

AN XY:

224540

show subpopulations

Gnomad4 AFR exome

AF:

0.00616

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.000190

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.0128

Gnomad4 NFE exome

AF:

0.000512

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00458

AC:

376

AN:

82128

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

100

AN XY:

19296

show subpopulations

Gnomad4 AFR

AF:

0.00997

Gnomad4 AMR

AF:

0.00345

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00287

Gnomad4 SAS

AF:

0.0233

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.00177

Gnomad4 OTH

AF:

0.00554

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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