X-105219970-C-G

Variant names:

• chrX-105219970-C-G
• rs782792744
• NM_031274.5:c.428G>C

Variant summary

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

The NM_031274.5(TEX13A):​c.428G>C​(p.Arg143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 112,750 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. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: TEX13A NM_031274.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• Publications: 0 publications found

Genes affected

TEX13A (HGNC:11735): (testis expressed 13A) This gene is similar to a mouse gene that is expressed in the testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

IL1RAPL2 (HGNC:5997): (interleukin 1 receptor accessory protein like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. This protein is similar to the interleukin 1 accessory proteins, and is most closely related to interleukin 1 receptor accessory protein-like 1 (IL1RAPL1). This gene and IL1RAPL1 are located at a region on chromosome X that is associated with X-linked non-syndromic cognitive disability. [provided by RefSeq, Jul 2008]

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=0.24853921).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031274.5. 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
	TEX13A	NM_031274.5	MANE Select	c.428G>C	p.Arg143Thr	missense	Exon 2 of 3	NP_112564.1	Q9BXU3
	IL1RAPL2	NM_017416.2	MANE Select	c.357-13848C>G		intron	N/A	NP_059112.1	Q9NP60
	TEX13A	NM_001291277.2		c.428G>C	p.Arg143Thr	missense	Exon 2 of 3	NP_001278206.1	Q9BXU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX13A	ENST00000600991.6	TSL:1 MANE Select	c.428G>C	p.Arg143Thr	missense	Exon 2 of 3	ENSP00000471604.2	Q9BXU3
	TEX13A	ENST00000609007.3	TSL:1	c.428G>C	p.Arg143Thr	missense	Exon 2 of 3	ENSP00000477478.2	Q9BXU3
	IL1RAPL2	ENST00000372582.6	TSL:1 MANE Select	c.357-13848C>G		intron	N/A	ENSP00000361663.1	Q9NP60

Frequencies

GnomAD3 genomes AF: 0.00000887 AC: 1 AN: 112750 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 9.21e-7 AC: 1 AN: 1085689 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 1 AN XY: 354375

African (AFR) AF: 0.00 AC: 0 AN: 26205

American (AMR) AF: 0.00 AC: 0 AN: 34657

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18677

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30071

South Asian (SAS) AF: 0.00 AC: 0 AN: 52489

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38327

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4087

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 835615

Other (OTH) AF: 0.00 AC: 0 AN: 45561

GnomAD4 genome AF: 0.00000887 AC: 1 AN: 112750 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34896

African (AFR) AF: 0.0000322 AC: 1 AN: 31058

American (AMR) AF: 0.00 AC: 0 AN: 10783

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3529

South Asian (SAS) AF: 0.00 AC: 0 AN: 2775

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6295

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53232

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.9
DANN	Benign	0.88
DEOGEN2	Benign	0.37	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.93
PrimateAI	Benign	0.36	T
Sift4G	Uncertain	0.022	D
Polyphen		0.84	P
Vest4		0.51
MutPred		0.28		Gain of phosphorylation at R143 (P = 0.0441)
MVP		0.055
ClinPred		0.22	T
GERP RS		-0.073
Varity_R		0.068
gMVP		0.22
Mutation Taster		=100/0	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: rs782792744; hg19: chrX-104464654;