Genetic Variant NM_001136234.3:c.1021T>C (chrX-24363781-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -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

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

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.1021T>C	p.Leu341Leu	synonymous	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.1021T>C	p.Leu341Leu	synonymous	Exon 1 of 1	ENSP00000509731.1	A0A7I2YQ69
	SUPT20HL1	ENST00000436466.2	TSL:6	c.1021T>C	p.Leu341Leu	synonymous	Exon 2 of 2	ENSP00000502907.1	A0A7I2YQ69

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

111795

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000469

AC:

AN:

181216

AF XY:

0.000488

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 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

African (AFR)

AF:

0.00

AC:

AN:

8420

American (AMR)

AF:

0.00

AC:

AN:

28772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8763

East Asian (EAS)

AF:

0.00622

AC:

AN:

9804

South Asian (SAS)

AF:

0.000476

AC:

AN:

39920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24370

Middle Eastern (MID)

AF:

0.000473

AC:

AN:

2116

European-Non Finnish (NFE)

AF:

0.000114

AC:

AN:

139747

Other (OTH)

AF:

0.000403

AC:

AN:

12420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000277

AC:

AN:

111849

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

34051

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30846

American (AMR)

AF:

0.00

AC:

AN:

10613

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2630

East Asian (EAS)

AF:

0.00593

AC:

AN:

3542

South Asian (SAS)

AF:

0.000390

AC:

AN:

2564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6133

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

53095

Other (OTH)

AF:

0.000656

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000261

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.30

(source)

DANN

Benign

0.45

PhyloP100

-0.038

Splicing

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

Publications

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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