19-14564260-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_138501.6(TECR):c.462C>A(p.Gly154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00635 in 1,606,628 control chromosomes in the GnomAD database, including 586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (281 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (305 hom.)
• Consequence: TECR NM_138501.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.447

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019727647).
• BP6: Variant 19-14564260-C-A is Benign according to our data. Variant chr19-14564260-C-A is described in ClinVar as [Benign]. Clinvar id is 130580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.447 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECR	NM_138501.6	c.462C>A	p.Gly154=	synonymous_variant	7/13	ENST00000215567.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECR	ENST00000215567.10	c.462C>A	p.Gly154=	synonymous_variant	7/13	1	NM_138501.6	P1

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5000 AN: 151764 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00899 AC: 2214 AN: 246254 Hom.: 130 AF XY: 0.00647 AC XY: 864 AN XY: 133618

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.00625

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00355 AC: 5171 AN: 1454746 Hom.: 305 Cov.: 34 AF XY: 0.00304 AC XY: 2202 AN XY: 724000

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.00635

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000216

Gnomad4 OTH exome AF: 0.00840

GnomAD4 genome AF: 0.0331 AC: 5033 AN: 151882 Hom.: 281 Cov.: 32 AF XY: 0.0321 AC XY: 2379 AN XY: 74212

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0247 Hom.: 60

Bravo AF: 0.0386

ESP6500AA AF: 0.122 AC: 537

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0107 AC: 1301

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

TECR-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 27, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	12
Dann	Benign	0.90
DEOGEN2	Benign	0.093	T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0020	T
MutationTaster	Benign	1.0	D;D
Sift4G	Pathogenic	0.0	D
GERP RS		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs76484116; hg19: chr19-14675072;