NM_001136234.3:c.1540_1551delGCTGCTGCTGCT

Variant names:

• chrX-24364256-TTGCTGCTGCTGC-T
• rs35206911
• NM_001136234.3:c.1540_1551delGCTGCTGCTGCT

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_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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: 0.439
• 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 = 0.00458 (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 the male GnomAd4 subpopulation. Median coverage is 2. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 100 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_1551delGCTGCTGCTGCT	p.Ala514_Ala517del	conservative_inframe_deletion	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_1551delGCTGCTGCTGCT	p.Ala514_Ala517del	conservative_inframe_deletion	Exon 1 of 1	ENSP00000509731.1	A0A7I2YQ69
	SUPT20HL1	ENST00000436466.2	TSL:6	c.1540_1551delGCTGCTGCTGCT	p.Ala514_Ala517del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000502907.1	A0A7I2YQ69

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 377 AN: 82121 Hom.: 1 Cov.: 2

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.: 11 AF XY: 0.00222 AC XY: 499 AN XY: 224540

African (AFR) AF: 0.00616 AC: 95 AN: 15427

American (AMR) AF: 0.00187 AC: 50 AN: 26680

Ashkenazi Jewish (ASJ) AF: 0.000190 AC: 3 AN: 15762

East Asian (EAS) AF: 0.00134 AC: 33 AN: 24562

South Asian (SAS) AF: 0.0125 AC: 512 AN: 41009

European-Finnish (FIN) AF: 0.0128 AC: 463 AN: 36054

Middle Eastern (MID) AF: 0.000608 AC: 2 AN: 3287

European-Non Finnish (NFE) AF: 0.000512 AC: 269 AN: 525291

Other (OTH) AF: 0.00181 AC: 59 AN: 32574

GnomAD4 genome AF: 0.00458 AC: 376 AN: 82128 Hom.: 1 Cov.: 2 AF XY: 0.00518 AC XY: 100 AN XY: 19296

African (AFR) AF: 0.00997 AC: 173 AN: 17345

American (AMR) AF: 0.00345 AC: 27 AN: 7823

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2061

East Asian (EAS) AF: 0.00287 AC: 8 AN: 2792

South Asian (SAS) AF: 0.0233 AC: 32 AN: 1371

European-Finnish (FIN) AF: 0.0122 AC: 51 AN: 4176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 183

European-Non Finnish (NFE) AF: 0.00177 AC: 79 AN: 44727

Other (OTH) AF: 0.00554 AC: 6 AN: 1084

Alfa AF: 0.00 Hom.: 142

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	3	-	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44

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;