X-149931042-C-T

Position:

• chrX-149931042-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.939C>T​(p.Tyr313=) 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 0.0023 (1 hom., 29 hem., cov: 20)
  • Exomes 𝑓: 0.00026 (1 hom. 94 hem.)
  • Failed GnomAD Quality Control
• Consequence: HSFX4 NM_001351114.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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=-0.97).
• BP6: Variant X-149931042-C-T is Benign according to our data. Variant chrX-149931042-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSFX4	NM_001351114.2	c.939C>T	p.Tyr313=	synonymous_variant	2/2	ENST00000457775.3	NP_001338043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSFX4	ENST00000457775.3	c.939C>T	p.Tyr313=	synonymous_variant	2/2	3	NM_001351114.2	ENSP00000489814	P1
EOLA2	ENST00000462691.5	c.433-961G>A		intron_variant		3		ENSP00000417546

Frequencies

GnomAD3 genomes AF: 0.00 AC: 253 AN: 111555 Hom.: 1 Cov.: 20 AF XY: 0.000857 AC XY: 29 AN XY: 33833 FAILED QC

Gnomad AFR AF: 0.00690

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000945

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000564

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000490

Gnomad OTH AF: 0.00267

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000265 AC: 218 AN: 824030 Hom.: 1 Cov.: 30 AF XY: 0.000369 AC XY: 94 AN XY: 254434

Gnomad4 AFR exome AF: 0.00303

Gnomad4 AMR exome AF: 0.00140

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00328

Gnomad4 SAS exome AF: 0.000141

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.000356

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00227 AC: 253 AN: 111604 Hom.: 1 Cov.: 20 AF XY: 0.000856 AC XY: 29 AN XY: 33894

Gnomad4 AFR AF: 0.00688

Gnomad4 AMR AF: 0.000944

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000565

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000490

Gnomad4 OTH AF: 0.00264

Alfa AF: 0.00159 Hom.: 6

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

Dec 01, 2022

HSFX4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs375322718; hg19: chrX-149099260;