7-98217500-C-T

Variant names:

• chr7-98217500-C-T
• rs1798041763
• NM_015395.3:c.3388G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015395.3(TECPR1):​c.3388G>A​(p.Gly1130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,450,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TECPR1 NM_015395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

TECPR1 (HGNC:22214): (tectonin beta-propeller repeat containing 1) This gene encodes a tethering factor involved in autophagy. The encoded protein is found at autolysosomes, and is involved in targeting protein aggregates, damaged mitochondria, and bacterial pathogens for autophagy [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR1	NM_015395.3	c.3388G>A	p.Gly1130Ser	missense_variant	Exon 26 of 26	ENST00000447648.7	NP_056210.1
TECPR1	XM_005250253.5	c.3388G>A	p.Gly1130Ser	missense_variant	Exon 26 of 26		XP_005250310.1
TECPR1	XM_017011937.2	c.3286G>A	p.Gly1096Ser	missense_variant	Exon 25 of 25		XP_016867426.1
TECPR1	XM_047420119.1	c.3286G>A	p.Gly1096Ser	missense_variant	Exon 25 of 25		XP_047276075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECPR1	ENST00000447648.7	c.3388G>A	p.Gly1130Ser	missense_variant	Exon 26 of 26	1	NM_015395.3	ENSP00000404923.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1450836 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720720

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000542

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3388G>A (p.G1130S) alteration is located in exon 26 (coding exon 24) of the TECPR1 gene. This alteration results from a G to A substitution at nucleotide position 3388, causing the glycine (G) at amino acid position 1130 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.32
Sift	Benign	0.035	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.56		Gain of MoRF binding (P = 0.1014);
MVP		0.66
MPC		0.69
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.23
gMVP		0.62

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: rs1798041763; hg19: chr7-97846812;