rs12434098

Positions:

• chr14-102402141-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014844.5(TECPR2):​c.220-5197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,070 control chromosomes in the GnomAD database, including 10,352 homozygotes. 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: 𝑓 0.36 (10352 hom., cov: 32)
• Consequence: TECPR2 NM_014844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

Genes affected

TECPR2 (HGNC:19957): (tectonin beta-propeller repeat containing 2) The protein encoded by this gene is a member of the tectonin beta-propeller repeat-containing (TECPR) family, and contains both TECPR and tryptophan-aspartic acid repeat (WD repeat) domains. This gene has been implicated in autophagy, as reduced expression levels of this gene have been associated with impaired autophagy. Recessive mutations in this gene have been associated with a hereditary form of spastic paraparesis (HSP). HSP is characterized by progressive spasticity and paralysis of the legs. There is also some evidence linking mutations in this gene with birdshot chorioretinopathy (BSCR), which results in inflammation of the choroid and retina. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECPR2	NM_014844.5	c.220-5197T>C		intron_variant		ENST00000359520.12	NP_055659.2
TECPR2	NM_001172631.3	c.220-5197T>C		intron_variant			NP_001166102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12	c.220-5197T>C		intron_variant		1	NM_014844.5	ENSP00000352510	P1
TECPR2	ENST00000558678.1	c.220-5197T>C		intron_variant		1		ENSP00000453671
TECPR2	ENST00000561228.1	n.348-5197T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55434 AN: 151952 Hom.: 10344 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55470 AN: 152070 Hom.: 10352 Cov.: 32 AF XY: 0.358 AC XY: 26641 AN XY: 74360

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.385

Alfa AF: 0.395 Hom.: 2446

Bravo AF: 0.362

Asia WGS AF: 0.279 AC: 972 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.92
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs12434098; hg19: chr14-102868478;