rs113855270

Variant names:

• chr19-14562510-G-A
• rs113855270
• ENST00000596073.6:c.115G>A
• TECR p.Val39Ile

Variant summary

Our verdict is Benign. The variant received -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. 8/10 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: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.84
• Publications: 1 publications found

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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 212393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000596073.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	NM_138501.6	MANE Select	c.16-15G>A		intron	N/A	NP_612510.1	Q9NZ01-1
	TECR	NM_001321170.1		c.61-15G>A		intron	N/A	NP_001308099.1	Q9NZ01
	TECR	NR_038103.2		n.119-15G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	ENST00000596073.6	TSL:1	c.115G>A	p.Val39Ile	missense	Exon 1 of 12	ENSP00000472697.2	M0R2N5
	TECR	ENST00000215567.10	TSL:1 MANE Select	c.16-15G>A		intron	N/A	ENSP00000215567.4	Q9NZ01-1
	TECR	ENST00000971295.1		c.217-15G>A		intron	N/A	ENSP00000641354.1

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

GnomAD2 exomes AF: 0.00539 AC: 1356 AN: 251446 AF XY: 0.00570

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 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

African (AFR) AF: 0.00194 AC: 65 AN: 33478

American (AMR) AF: 0.00559 AC: 250 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00823 AC: 215 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00226 AC: 195 AN: 86258

European-Finnish (FIN) AF: 0.00129 AC: 69 AN: 53420

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5768

European-Non Finnish (NFE) AF: 0.0104 AC: 11561 AN: 1111922

Other (OTH) AF: 0.00906 AC: 547 AN: 60392

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

African (AFR) AF: 0.00204 AC: 85 AN: 41594

American (AMR) AF: 0.00706 AC: 108 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.000470 AC: 5 AN: 10632

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00942 AC: 641 AN: 68032

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00653 Hom.: 0

Bravo AF: 0.00645

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Intellectual disability, autosomal recessive 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
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
PhyloP100		1.8
PromoterAI		-0.051	Neutral
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs113855270;

hg19: chr19-14673322;