rs117833765

chr19-14564848-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_138501.6(TECR):c.552C>T(p.Tyr184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,613,980 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00076 (14 hom.)
• Consequence: TECR NM_138501.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.534

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009176761).
• BP6: Variant 19-14564848-C-T is Benign according to our data. Variant chr19-14564848-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 436973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-14564848-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.534 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECR	NM_138501.6	c.552C>T	p.Tyr184=	synonymous_variant	8/13	ENST00000215567.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECR	ENST00000215567.10	c.552C>T	p.Tyr184=	synonymous_variant	8/13	1	NM_138501.6	P1

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152050 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00127 AC: 320 AN: 251416 Hom.: 3 AF XY: 0.00178 AC XY: 242 AN XY: 135912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00882

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000760 AC: 1111 AN: 1461812 Hom.: 14 Cov.: 34 AF XY: 0.00110 AC XY: 798 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00984

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000144

Gnomad4 OTH exome AF: 0.000993

GnomAD4 genome AF: 0.000355 AC: 54 AN: 152168 Hom.: 0 Cov.: 30 AF XY: 0.000511 AC XY: 38 AN XY: 74374

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000360 Hom.: 0

Bravo AF: 0.000242

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00139 AC: 169

EpiCase AF: 0.000491

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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

May 05, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

TECR: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	8.6
Dann	Benign	0.79
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0092	T
MutationTaster	Benign	1.0	D;D
Sift4G	Benign	0.93	T
MVP		0.81
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs117833765; hg19: chr19-14675660;