Genetic Variant HSFX4:p.Asn102Asn (chrX-149929950-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001351114.2(HSFX4):c.306C>T(p.Asn102Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., 49 hem., cov: 17)

Exomes 𝑓: 0.0035 ( 14 hom. 995 hem. )

Failed GnomAD Quality Control

Consequence

HSFX4
NM_001351114.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.85

Publications

0 publications found

Variant links:

Genes affected

HSFX4 (HGNC:52398): (heat shock transcription factor family, X-linked member 4) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HSFX4 links:

EOLA2 (HGNC:17402): (endothelium and lymphocyte associated ASCH domain 2)

EOLA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant X-149929950-C-T is Benign according to our data. Variant chrX-149929950-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661623.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.85 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351114.2. 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
	HSFX4	NM_001351114.2	MANE Select	c.306C>T	p.Asn102Asn	synonymous	Exon 1 of 2	NP_001338043.1	A0A1B0GTS1
	EOLA2	NM_001437940.1		c.*123G>A		3_prime_UTR	Exon 6 of 6	NP_001424869.1	Q5HY62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSFX4	ENST00000457775.3	TSL:3 MANE Select	c.306C>T	p.Asn102Asn	synonymous	Exon 1 of 2	ENSP00000489814.2	A0A1B0GTS1
	EOLA2	ENST00000462691.5	TSL:3	c.*123G>A		3_prime_UTR	Exon 6 of 6	ENSP00000417546.1	Q5HY62

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

293

AN:

97090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.000800

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00358

Gnomad OTH

AF:

0.00157

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00348

AC:

3331

AN:

955891

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

995

AN XY:

291083

show subpopulations

African (AFR)

AF:

0.00571

AC:

114

AN:

19977

American (AMR)

AF:

0.000736

AC:

AN:

13590

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

13775

East Asian (EAS)

AF:

0.00

AC:

AN:

25237

South Asian (SAS)

AF:

0.0000275

AC:

AN:

36414

European-Finnish (FIN)

AF:

0.000474

AC:

AN:

33765

Middle Eastern (MID)

AF:

0.000276

AC:

AN:

3617

European-Non Finnish (NFE)

AF:

0.00396

AC:

3051

AN:

769487

Other (OTH)

AF:

0.00297

AC:

119

AN:

40029

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

104

208

313

417

521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00302

AC:

293

AN:

97127

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

AN XY:

22665

show subpopulations

African (AFR)

AF:

0.00431

AC:

104

AN:

24127

American (AMR)

AF:

0.000785

AC:

AN:

8921

Ashkenazi Jewish (ASJ)

AF:

0.000800

AC:

AN:

2500

East Asian (EAS)

AF:

0.00

AC:

AN:

3163

South Asian (SAS)

AF:

0.00

AC:

AN:

1990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4491

Middle Eastern (MID)

AF:

0.00

AC:

AN:

201

European-Non Finnish (NFE)

AF:

0.00358

AC:

178

AN:

49782

Other (OTH)

AF:

0.00154

AC:

AN:

1295

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00508

Hom.:

Bravo

AF:

0.00315

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

-1.0

CADD

Benign

0.16

(source)

DANN

Benign

0.73

PhyloP100

-2.9

PromoterAI

-0.0045

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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