X-149929950-C-T

Position:

• chrX-149929950-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001351114.2(HSFX4):​c.306C>T​(p.Asn102=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.85

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]

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

ACMG classification

Verdict is Benign. Variant got -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 id is 2661623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.85 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSFX4	NM_001351114.2	c.306C>T	p.Asn102=	synonymous_variant	1/2	ENST00000457775.3	NP_001338043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSFX4	ENST00000457775.3	c.306C>T	p.Asn102=	synonymous_variant	1/2	3	NM_001351114.2	ENSP00000489814	P1
EOLA2	ENST00000462691.5	c.*123G>A		3_prime_UTR_variant	6/6	3		ENSP00000417546

Frequencies

GnomAD3 genomes AF: 0.00 AC: 293 AN: 97090 Hom.: 1 Cov.: 17 AF XY: 0.00217 AC XY: 49 AN XY: 22622 FAILED QC

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.: 14 Cov.: 23 AF XY: 0.00342 AC XY: 995 AN XY: 291083

Gnomad4 AFR exome AF: 0.00571

Gnomad4 AMR exome AF: 0.000736

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000275

Gnomad4 FIN exome AF: 0.000474

Gnomad4 NFE exome AF: 0.00396

Gnomad4 OTH exome AF: 0.00297

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00302 AC: 293 AN: 97127 Hom.: 1 Cov.: 17 AF XY: 0.00216 AC XY: 49 AN XY: 22665

Gnomad4 AFR AF: 0.00431

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.000800

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00358

Gnomad4 OTH AF: 0.00154

Alfa AF: 0.00508 Hom.: 20

Bravo AF: 0.00315

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

HSFX4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs782370593; hg19: chrX-149098168;