3-14064854-C-A

Variant names:

• chr3-14064854-C-A
• rs763643679
• ENST00000326972.12:n.1039C>A

Variant summary

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

The ENST00000326972.12(TPRXL):​n.1039C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 156,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: TPRXL ENST00000326972.12 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.86
• Publications: 0 publications found

Genes affected

TPRXL (HGNC:):

TPRXL (HGNC:32178): (tetrapeptide repeat homeobox like (pseudogene)) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This pseudogene is a member of the TPRX homeobox gene family. [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 (REVEL=0.031).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326972.12. 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
	TPRXL	NR_002223.3		n.1133C>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRXL	ENST00000326972.12	TSL:2	n.1039C>A		non_coding_transcript_exon	Exon 3 of 3
	TPRXL	ENST00000424053.5	TSL:3	n.1225C>A		non_coding_transcript_exon	Exon 3 of 3
	TPRXL	ENST00000429201.6	TSL:2	n.1125C>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000639 AC: 1 AN: 156542 Hom.: 0 Cov.: 0 AF XY: 0.0000115 AC XY: 1 AN XY: 87166

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5628

American (AMR) AF: 0.00 AC: 0 AN: 12890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4734

East Asian (EAS) AF: 0.00 AC: 0 AN: 6882

South Asian (SAS) AF: 0.00 AC: 0 AN: 29574

European-Finnish (FIN) AF: 0.000161 AC: 1 AN: 6214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1880

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 81142

Other (OTH) AF: 0.00 AC: 0 AN: 7598

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.5
DANN	Benign	0.30
PhyloP100		-4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs763643679;

hg19: chr3-14106354;