3-14064854-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000326972.12(TPRXL):​n.1039C>T 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 0.000083 in 72,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000083 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPRXL ENST00000326972.12 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 3-14064854-C-T is Benign according to our data. Variant chr3-14064854-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653576.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T		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>T		non_coding_transcript_exon	Exon 3 of 3
	TPRXL	ENST00000424053.5	TSL:3	n.1225C>T		non_coding_transcript_exon	Exon 3 of 3
	TPRXL	ENST00000429201.6	TSL:2	n.1125C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0000830 AC: 6 AN: 72294 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000168

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: 0.0000335

Gnomad OTH AF: 0.00107

GnomAD2 exomes AF: 0.000193 AC: 18 AN: 93336 AF XY: 0.000178

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000504

Gnomad EAS exome AF: 0.000853

Gnomad FIN exome AF: 0.000938

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000160 AC: 25 AN: 156510 Hom.: 0 Cov.: 0 AF XY: 0.000161 AC XY: 14 AN XY: 87144

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

African (AFR) AF: 0.000178 AC: 1 AN: 5626

American (AMR) AF: 0.000155 AC: 2 AN: 12888

Ashkenazi Jewish (ASJ) AF: 0.000211 AC: 1 AN: 4732

East Asian (EAS) AF: 0.000581 AC: 4 AN: 6882

South Asian (SAS) AF: 0.0000676 AC: 2 AN: 29568

European-Finnish (FIN) AF: 0.000805 AC: 5 AN: 6212

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

European-Non Finnish (NFE) AF: 0.0000986 AC: 8 AN: 81126

Other (OTH) AF: 0.000263 AC: 2 AN: 7596

⚠️ 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 AF: 0.0000830 AC: 6 AN: 72294 Hom.: 0 Cov.: 23 AF XY: 0.0000856 AC XY: 3 AN XY: 35048

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

African (AFR) AF: 0.000168 AC: 4 AN: 23860

American (AMR) AF: 0.00 AC: 0 AN: 6936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1588

East Asian (EAS) AF: 0.00 AC: 0 AN: 2902

South Asian (SAS) AF: 0.00 AC: 0 AN: 1982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.0000335 AC: 1 AN: 29832

Other (OTH) AF: 0.00107 AC: 1 AN: 932

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0143708), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0522 Hom.: 0

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	-0.68
CADD	Benign	3.5
DANN	Benign	0.41
PhyloP100		-4.9
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: rs763643679; hg19: chr3-14106354; COSMIC: COSV58897191;