X-149548464-G-A

Variant names:

• chrX-149548464-G-A
• rs1175140157
• NM_001323079.3:c.930C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.479
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -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 VariationId is 3251113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.479 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323079.3. 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
	HSFX3	NM_001323079.3	MANE Select	c.930C>T	p.Ile310Ile	synonymous	Exon 2 of 2	NP_001310008.1	A0A1B0GWH4
	EOLA1	NM_001171909.4		c.433-952G>A		intron	N/A	NP_001165380.1	Q8TE69-2
	EOLA1	NM_001324276.2		c.433-952G>A		intron	N/A	NP_001311205.1	Q8TE69-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSFX3	ENST00000431993.4	TSL:3 MANE Select	c.930C>T	p.Ile310Ile	synonymous	Exon 2 of 2	ENSP00000490928.1	A0A1B0GWH4
	EOLA1	ENST00000422892.2	TSL:2	c.433-952G>A		intron	N/A	ENSP00000422312.1	Q8TE69-2
	EOLA1	ENST00000434353.6	TSL:5	c.433-952G>A		intron	N/A	ENSP00000423160.1	Q8TE69-2

Frequencies

GnomAD3 genomes AF: 0.00000905 AC: 1 AN: 110532 Hom.: 0 Cov.: 19

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.: 30

GnomAD4 genome AF: 0.00000905 AC: 1 AN: 110532 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 32924

African (AFR) AF: 0.00 AC: 0 AN: 30147

American (AMR) AF: 0.0000953 AC: 1 AN: 10494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2579

East Asian (EAS) AF: 0.00 AC: 0 AN: 3560

South Asian (SAS) AF: 0.00 AC: 0 AN: 2597

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5995

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52777

Other (OTH) AF: 0.00 AC: 0 AN: 1470

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.51
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs1175140157; hg19: chrX-148630009;