X-24364256-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chrX-24364256-T-TTGCTGCTGCTGC
• rs35206911
• NM_001136234.3:c.1540_1551dupGCTGCTGCTGCT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001136234.3(SUPT20HL1):​c.1540_1551dupGCTGCTGCTGCT​(p.Ala514_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 0.012 (13 hom., 217 hem., cov: 2)
  • Exomes 𝑓: 0.012 (213 hom. 1655 hem.)
  • Failed GnomAD Quality Control
• Consequence: SUPT20HL1 NM_001136234.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 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 = 0.0118 (970/82116) while in subpopulation SAS AF = 0.0292 (40/1372). AF 95% confidence interval is 0.022. There are 13 homozygotes in GnomAd4. There are 217 alleles in the male GnomAd4 subpopulation. Median coverage is 2. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 gene

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.1540_1551dupGCTGCTGCTGCT	p.Ala514_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.1540_1551dupGCTGCTGCTGCT	p.Ala514_Ala517dup	conservative_inframe_insertion	Exon 1 of 1	ENSP00000509731.1	A0A7I2YQ69
	SUPT20HL1	ENST00000436466.2	TSL:6	c.1540_1551dupGCTGCTGCTGCT	p.Ala514_Ala517dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000502907.1	A0A7I2YQ69

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 969 AN: 82108 Hom.: 13 Cov.: 2

Gnomad AFR AF: 0.00999

Gnomad AMI AF: 0.00177

Gnomad AMR AF: 0.00985

Gnomad ASJ AF: 0.00243

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.0200

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0103

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0118 AC: 8501 AN: 717730 Hom.: 213 Cov.: 18 AF XY: 0.00745 AC XY: 1655 AN XY: 222044

African (AFR) AF: 0.0110 AC: 171 AN: 15482

American (AMR) AF: 0.0137 AC: 363 AN: 26529

Ashkenazi Jewish (ASJ) AF: 0.00292 AC: 46 AN: 15745

East Asian (EAS) AF: 0.0168 AC: 413 AN: 24621

South Asian (SAS) AF: 0.0158 AC: 638 AN: 40273

European-Finnish (FIN) AF: 0.0109 AC: 391 AN: 35975

Middle Eastern (MID) AF: 0.0126 AC: 41 AN: 3259

European-Non Finnish (NFE) AF: 0.0115 AC: 6034 AN: 523409

Other (OTH) AF: 0.0125 AC: 404 AN: 32437

GnomAD4 genome AF: 0.0118 AC: 970 AN: 82116 Hom.: 13 Cov.: 2 AF XY: 0.0112 AC XY: 217 AN XY: 19290

African (AFR) AF: 0.0100 AC: 174 AN: 17354

American (AMR) AF: 0.00984 AC: 77 AN: 7823

Ashkenazi Jewish (ASJ) AF: 0.00243 AC: 5 AN: 2061

East Asian (EAS) AF: 0.0151 AC: 42 AN: 2789

South Asian (SAS) AF: 0.0292 AC: 40 AN: 1372

European-Finnish (FIN) AF: 0.00838 AC: 35 AN: 4176

Middle Eastern (MID) AF: 0.0219 AC: 4 AN: 183

European-Non Finnish (NFE) AF: 0.0130 AC: 581 AN: 44708

Other (OTH) AF: 0.0101 AC: 11 AN: 1084

Alfa AF: 0.00843 Hom.: 142

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

Other links and lift over

dbSNP: rs35206911; hg19: chrX-24382373;