chrX-104250394-G-T

Variant names:

• chrX-104250394-G-T
• rs1923136187
• NM_153448.4:c.1055C>A

Variant summary

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

The NM_153448.4(ESX1):​c.1055C>A​(p.Pro352Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ESX1 NM_153448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.761
• Publications: 0 publications found

Genes affected

ESX1 (HGNC:14865): (ESX homeobox 1) This gene encodes a dual-function 65 kDa protein that undergoes proteolytic cleavage to produce a 45 kDa N-terminal fragment with a paired-like homeodomain and a 20 kDa C-terminal fragment with a proline-rich domain. The C-terminal fragment localizes to the cytoplasm while the N-terminal fragment localizes exclusively to the nucleus. In contrast to human, the mouse homolog has a novel PN/PF motif in the C-terminus and is paternally imprinted in placental tissue. This gene likely plays a role in placental development and spermatogenesis. [provided by RefSeq, Jan 2010]

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=0.09785169).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153448.4. 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
	ESX1	NM_153448.4	MANE Select	c.1055C>A	p.Pro352Gln	missense	Exon 4 of 4	NP_703149.1	Q8N693

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESX1	ENST00000372588.4	TSL:1 MANE Select	c.1055C>A	p.Pro352Gln	missense	Exon 4 of 4	ENSP00000361669.4	Q8N693

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 904805 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 276511

African (AFR) AF: 0.00 AC: 0 AN: 18395

American (AMR) AF: 0.00 AC: 0 AN: 7995

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11309

East Asian (EAS) AF: 0.00 AC: 0 AN: 21335

South Asian (SAS) AF: 0.00 AC: 0 AN: 26982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 750099

Other (OTH) AF: 0.00 AC: 0 AN: 36982

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.8
DANN	Benign	0.93
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.76
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.13
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.015	D
Polyphen		0.16	B
Vest4		0.14
MutPred		0.29		Loss of glycosylation at P352 (P = 0.0135)
MVP		0.36
MPC		0.37
ClinPred		0.080	T
GERP RS		-3.0
Varity_R		0.042
gMVP		0.13
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1923136187; hg19: chrX-103495075;