Variant chrX-149548464-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001323079.3(HSFX3):c.930C>T(p.Ile310Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000905 in 110,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 19)

Consequence

HSFX3
NM_001323079.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.479

Variant links:

Genes affected

HSFX3 (HGNC:52395): (heat shock transcription factor family, X-linked member 3) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific 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 part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HSFX3 links:

EOLA1 (HGNC:28089): (endothelium and lymphocyte associated ASCH domain 1) Involved in regulation of interleukin-6 production. [provided by Alliance of Genome Resources, Apr 2022]

EOLA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-149548464-G-A is Benign according to our data. Variant chrX-149548464-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3251113.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.479 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSFX3	NM_001323079.3 linkuse as main transcript	c.930C>T	p.Ile310Ile	synonymous_variant	2/2	ENST00000431993.4	NP_001310008.1	A0A1B0GWH4
EOLA1	NM_001171909.4 linkuse as main transcript	c.433-952G>A		intron_variant			NP_001165380.1	Q8TE69-2
EOLA1	NM_001324276.2 linkuse as main transcript	c.433-952G>A		intron_variant			NP_001311205.1	Q8TE69-2
EOLA1	NM_001324279.2 linkuse as main transcript	c.433-952G>A		intron_variant			NP_001311208.1	Q8TE69-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HSFX3	ENST00000431993.4 linkuse as main transcript	c.930C>T	p.Ile310Ile	synonymous_variant	2/2	3	NM_001323079.3	ENSP00000490928.1	A0A1B0GWH4
EOLA1	ENST00000422892.2 linkuse as main transcript	c.433-952G>A		intron_variant		2		ENSP00000422312.1	Q8TE69-2
EOLA1	ENST00000434353.6 linkuse as main transcript	c.433-952G>A		intron_variant		5		ENSP00000423160.1	Q8TE69-2
EOLA1	ENST00000514208.5 linkuse as main transcript	c.433-952G>A		intron_variant		5		ENSP00000423708.1	Q8TE69-2

Frequencies

GnomAD3 genomes

AF:

0.00000905

AC:

AN:

110532

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32924

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000953

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000905

AC:

AN:

110532

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32924

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000953

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

HSFX3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.37

DANN

Benign

0.51

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over