chrX-149548464-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001323079.3(HSFX3):​c.930C>G​(p.Ile310Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000122 in 820,574 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. 7/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I310I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: HSFX3 NM_001323079.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08639026).

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>G	p.Ile310Met	missense	Exon 2 of 2	NP_001310008.1	A0A1B0GWH4
	EOLA1	NM_001171909.4		c.433-952G>C		intron	N/A	NP_001165380.1	Q8TE69-2
	EOLA1	NM_001324276.2		c.433-952G>C		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>G	p.Ile310Met	missense	Exon 2 of 2	ENSP00000490928.1	A0A1B0GWH4
	EOLA1	ENST00000422892.2	TSL:2	c.433-952G>C		intron	N/A	ENSP00000422312.1	Q8TE69-2
	EOLA1	ENST00000434353.6	TSL:5	c.433-952G>C		intron	N/A	ENSP00000423160.1	Q8TE69-2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000122 AC: 1 AN: 820574 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 250692

African (AFR) AF: 0.00 AC: 0 AN: 17888

American (AMR) AF: 0.00 AC: 0 AN: 6444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10431

East Asian (EAS) AF: 0.0000490 AC: 1 AN: 20389

South Asian (SAS) AF: 0.00 AC: 0 AN: 14153

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16403

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2010

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 699284

Other (OTH) AF: 0.00 AC: 0 AN: 33572

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.53
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.086	T
PhyloP100		-0.48
GERP RS		-1.7
Varity_R		0.10
gMVP		0.090
Mutation Taster		=100/0	polymorphism

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;