rs1190547

Variant names:

• chr14-102438750-G-C
• rs1190547
• NM_014844.5:c.2578+545G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014844.5(TECPR2):​c.2578+545G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,026 control chromosomes in the GnomAD database, including 7,139 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 0.29 (7139 hom., cov: 32)
• Consequence: TECPR2 NM_014844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 3 publications found

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]

TECPR2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 49

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR2	NM_014844.5	c.2578+545G>C		intron_variant	Intron 10 of 19	ENST00000359520.12	NP_055659.2
TECPR2	NM_001172631.3	c.2578+545G>C		intron_variant	Intron 10 of 16		NP_001166102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12	c.2578+545G>C		intron_variant	Intron 10 of 19	1	NM_014844.5	ENSP00000352510.7
TECPR2	ENST00000558678.1	c.2578+545G>C		intron_variant	Intron 10 of 16	1		ENSP00000453671.1
TECPR2	ENST00000557786.1	n.187+287G>C		intron_variant	Intron 1 of 3	4
TECPR2	ENST00000560060.5	n.374+545G>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44300 AN: 151910 Hom.: 7144 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.291 AC: 44295 AN: 152026 Hom.: 7139 Cov.: 32 AF XY: 0.295 AC XY: 21933 AN XY: 74272

African (AFR) AF: 0.155 AC: 6442 AN: 41486

American (AMR) AF: 0.279 AC: 4257 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1672 AN: 5164

South Asian (SAS) AF: 0.235 AC: 1135 AN: 4826

European-Finnish (FIN) AF: 0.448 AC: 4710 AN: 10520

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23896 AN: 67968

Other (OTH) AF: 0.303 AC: 641 AN: 2114

Alfa AF: 0.317 Hom.: 995

Bravo AF: 0.275

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.019
DANN	Benign	0.59
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1190547; hg19: chr14-102905087;