Genetic Variant TECR:p.Ala46Pro (chr19-14563675-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138501.6(TECR):c.136G>C(p.Ala46Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A46T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TECR
NM_138501.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

1 publications found

Variant links:

Genes affected

TECR (HGNC:4551): (trans-2,3-enoyl-CoA reductase) This gene encodes a multi-pass membrane protein that resides in the endoplasmic reticulum, and belongs to the steroid 5-alpha reductase family. The elongation of microsomal long and very long chain fatty acid consists of 4 sequential reactions. This protein catalyzes the final step, reducing trans-2,3-enoyl-CoA to saturated acyl-CoA. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Apr 2011]

TECR Gene-Disease associations (from GenCC):

autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
intellectual disability, autosomal recessive 14
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)

TECR links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18685451).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138501.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TECR	NM_138501.6	MANE Select	c.136G>C	p.Ala46Pro	missense	Exon 4 of 13	NP_612510.1	Q9NZ01-1
TECR	NM_001321170.1		c.181G>C	p.Ala61Pro	missense	Exon 5 of 14	NP_001308099.1	Q9NZ01
TECR	NR_038103.2		n.271G>C		non_coding_transcript_exon	Exon 4 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TECR	ENST00000215567.10	TSL:1 MANE Select	c.136G>C	p.Ala46Pro	missense	Exon 4 of 13	ENSP00000215567.4	Q9NZ01-1
TECR	ENST00000596073.6	TSL:1	c.250G>C	p.Ala84Pro	missense	Exon 3 of 12	ENSP00000472697.2	M0R2N5
TECR	ENST00000971295.1		c.337G>C	p.Ala113Pro	missense	Exon 5 of 14	ENSP00000641354.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.000156

AC:

AN:

243166

AF XY:

0.0000527

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000822

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1458582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725656

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4994

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111718

Other (OTH)

AF:

0.00

AC:

AN:

60220

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.033

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.77

MutationAssessor

Pathogenic

3.0

PhyloP100

7.6

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.33

Sift

Benign

0.24

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.83

MVP

0.56

MPC

2.4

ClinPred

0.20

GERP RS

5.5

Varity_R

0.46

gMVP

0.60

Mutation Taster

=35/65

disease causing

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over