Genetic Variant TECPR1:p.Arg1145Trp (chr7-98217455-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015395.3(TECPR1):c.3433C>T(p.Arg1145Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 1,609,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

TECPR1
NM_015395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0250

Publications

0 publications found

Variant links:

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]

TECPR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12460211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015395.3. 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
	TECPR1	NM_015395.3	MANE Select	c.3433C>T	p.Arg1145Trp	missense	Exon 26 of 26	NP_056210.1	Q7Z6L1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TECPR1	ENST00000447648.7	TSL:1 MANE Select	c.3433C>T	p.Arg1145Trp	missense	Exon 26 of 26	ENSP00000404923.2	Q7Z6L1-1
TECPR1	ENST00000490842.5	TSL:1	n.2631C>T		non_coding_transcript_exon	Exon 15 of 16
TECPR1	ENST00000871695.1		c.3433C>T	p.Arg1145Trp	missense	Exon 26 of 26	ENSP00000541754.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000506

AC:

AN:

237096

AF XY:

0.0000462

show subpopulations

Gnomad AFR exome

AF:

0.0000706

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000542

AC:

AN:

1457430

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

724688

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33436

American (AMR)

AF:

0.000180

AC:

AN:

44400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25960

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39606

South Asian (SAS)

AF:

0.0000467

AC:

AN:

85742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000576

AC:

AN:

1110438

Other (OTH)

AF:

0.00

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41442

American (AMR)

AF:

0.000589

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000971

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.78

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

PhyloP100

0.025

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.050

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.10

MutPred

0.29

Loss of disorder (P = 0.0527)

MVP

0.46

MPC

0.24

ClinPred

0.23

GERP RS

0.95

Varity_R

0.073

gMVP

0.51

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over