rs113855270

chr19-14562510-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000596073.6(TECR):c.115G>A(p.Val39Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 1,614,162 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (66 hom.)
• Consequence: TECR ENST00000596073.6 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.84

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009060264).
• BP6: Variant 19-14562510-G-A is Benign according to our data. Variant chr19-14562510-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECR	NM_138501.6	c.16-15G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000215567.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECR	ENST00000215567.10	c.16-15G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_138501.6	P1

Frequencies

GnomAD3 genomes AF: 0.00592 AC: 901 AN: 152250 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00944

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00539 AC: 1356 AN: 251446 Hom.: 3 AF XY: 0.00570 AC XY: 775 AN XY: 135906

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00512

Gnomad ASJ exome AF: 0.00784

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00212

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00845

Gnomad OTH exome AF: 0.00586

GnomAD4 exome AF: 0.00886 AC: 12948 AN: 1461794 Hom.: 66 Cov.: 31 AF XY: 0.00860 AC XY: 6252 AN XY: 727208

Gnomad4 AFR exome AF: 0.00194

Gnomad4 AMR exome AF: 0.00559

Gnomad4 ASJ exome AF: 0.00823

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00226

Gnomad4 FIN exome AF: 0.00129

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.00906

GnomAD4 genome AF: 0.00592 AC: 902 AN: 152368 Hom.: 3 Cov.: 33 AF XY: 0.00541 AC XY: 403 AN XY: 74512

Gnomad4 AFR AF: 0.00204

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000470

Gnomad4 NFE AF: 0.00942

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00653 Hom.: 0

Bravo AF: 0.00645

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0100 AC: 86

ExAC AF: 0.00553 AC: 671

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 22, 2015

- -

Intellectual disability, autosomal recessive 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 03, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

TECR: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
Cadd	Benign	20
Dann	Benign	0.86
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0091	T
MutationTaster	Benign	1.0	D;D
GERP RS		4.4

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

LitVar

Other links and lift over

dbSNP: rs113855270; hg19: chr19-14673322;