Genetic Variant TECR:p.Thr89Lys (chr19-14563902-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138501.6(TECR):c.266C>A(p.Thr89Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. T89M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TECR
NM_138501.6 missense, splice_region

Scores

Splicing: ADA: 0.9231

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.46

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.266C>A	p.Thr89Lys	missense splice_region	Exon 5 of 13	NP_612510.1	Q9NZ01-1
TECR	NM_001321170.1		c.311C>A	p.Thr104Lys	missense splice_region	Exon 6 of 14	NP_001308099.1	Q9NZ01
TECR	NR_038103.2		n.401C>A		splice_region non_coding_transcript_exon	Exon 5 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TECR	ENST00000215567.10	TSL:1 MANE Select	c.266C>A	p.Thr89Lys	missense splice_region	Exon 5 of 13	ENSP00000215567.4	Q9NZ01-1
TECR	ENST00000596073.6	TSL:1	c.380C>A	p.Thr127Lys	missense splice_region	Exon 4 of 12	ENSP00000472697.2	M0R2N5
TECR	ENST00000971295.1		c.467C>A	p.Thr156Lys	missense splice_region	Exon 6 of 14	ENSP00000641354.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

3.0

PhyloP100

7.5

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.41

Sift

Uncertain

0.029

Sift4G

Uncertain

0.054

Polyphen

0.15

Vest4

0.97

MVP

0.56

MPC

1.3

ClinPred

1.0

GERP RS

5.2

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.85

gMVP

0.85

Mutation Taster

=208/92

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.92

dbscSNV1_RF

Benign

0.66

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

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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