Genetic Variant SUPT20HL1:p.Ala509_Ala517dup (chrX-24364256-T-TTGCTGCTGCTGCTGCTGCTGCTGCTGC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001136234.3(SUPT20HL1):c.1525_1551dupGCTGCTGCTGCTGCTGCTGCTGCTGCT(p.Ala509_Ala517dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., 1 hem., cov: 2)

Exomes 𝑓: 0.000022 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

SUPT20HL1
NM_001136234.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.334

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001136234.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136234.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT20HL1	NM_001136234.3	MANE Select	c.1525_1551dupGCTGCTGCTGCTGCTGCTGCTGCTGCT	p.Ala509_Ala517dup	conservative_inframe_insertion	Exon 1 of 1	NP_001129706.3	A0A7I2YQ69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT20HL1	ENST00000686983.1	MANE Select	c.1525_1551dupGCTGCTGCTGCTGCTGCTGCTGCTGCT	p.Ala509_Ala517dup	conservative_inframe_insertion	Exon 1 of 1	ENSP00000509731.1	A0A7I2YQ69
	SUPT20HL1	ENST00000436466.2	TSL:6	c.1525_1551dupGCTGCTGCTGCTGCTGCTGCTGCTGCT	p.Ala509_Ala517dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000502907.1	A0A7I2YQ69

Frequencies

GnomAD3 genomes

AF:

0.0000365

AC:

AN:

82145

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000670

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000222

AC:

AN:

721814

Hom.:

Cov.:

AF XY:

0.00000887

AC XY:

AN XY:

225476

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

15567

American (AMR)

AF:

0.0000748

AC:

AN:

26742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15764

East Asian (EAS)

AF:

0.000121

AC:

AN:

24830

South Asian (SAS)

AF:

0.00

AC:

AN:

41345

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3290

European-Non Finnish (NFE)

AF:

0.0000209

AC:

AN:

525491

Other (OTH)

AF:

0.00

AC:

AN:

32643

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000770449), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.368

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

AF:

0.0000365

AC:

AN:

82145

Hom.:

Cov.:

AF XY:

0.0000519

AC XY:

AN XY:

19279

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17324

American (AMR)

AF:

0.00

AC:

AN:

7819

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2061

East Asian (EAS)

AF:

0.00

AC:

AN:

2797

South Asian (SAS)

AF:

0.00

AC:

AN:

1390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4177

Middle Eastern (MID)

AF:

0.00

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.0000670

AC:

AN:

44743

Other (OTH)

AF:

0.00

AC:

AN:

1068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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X-24364256-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over