chr19-14565817-G-A

Variant names:

• chr19-14565817-G-A
• rs147656694
• NM_138501.6:c.873G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_138501.6(TECR):​c.873G>A​(p.Lys291Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,600,642 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (5 hom.)
• Consequence: TECR NM_138501.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65
• Publications: 0 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 19-14565817-G-A is Benign according to our data. Variant chr19-14565817-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 212397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	NM_138501.6	MANE Select	c.873G>A	p.Lys291Lys	synonymous	Exon 13 of 13	NP_612510.1	Q9NZ01-1
	TECR	NM_001321170.1		c.918G>A	p.Lys306Lys	synonymous	Exon 14 of 14	NP_001308099.1	Q9NZ01
	TECR	NR_038103.2		n.1008G>A		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	ENST00000215567.10	TSL:1 MANE Select	c.873G>A	p.Lys291Lys	synonymous	Exon 13 of 13	ENSP00000215567.4	Q9NZ01-1
	TECR	ENST00000596073.6	TSL:1	c.987G>A	p.Lys329Lys	synonymous	Exon 12 of 12	ENSP00000472697.2	M0R2N5
	TECR	ENST00000971295.1		c.1074G>A	p.Lys358Lys	synonymous	Exon 14 of 14	ENSP00000641354.1

Frequencies

GnomAD3 genomes AF: 0.000999 AC: 152 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000319 AC: 71 AN: 222244 AF XY: 0.000231

Gnomad AFR exome AF: 0.00383

Gnomad AMR exome AF: 0.0000940

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000306

Gnomad OTH exome AF: 0.000363

GnomAD4 exome AF: 0.000141 AC: 204 AN: 1448350 Hom.: 5 Cov.: 34 AF XY: 0.000142 AC XY: 102 AN XY: 719750

African (AFR) AF: 0.00353 AC: 117 AN: 33168

American (AMR) AF: 0.000140 AC: 6 AN: 42712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 39076

South Asian (SAS) AF: 0.000696 AC: 59 AN: 84788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50580

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5652

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1106822

Other (OTH) AF: 0.000234 AC: 14 AN: 59786

GnomAD4 genome AF: 0.000998 AC: 152 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.000927 AC XY: 69 AN XY: 74462

African (AFR) AF: 0.00356 AC: 148 AN: 41580

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000555 Hom.: 0

Bravo AF: 0.00124

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.3
DANN	Benign	0.87
PhyloP100		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs147656694; hg19: chr19-14676629;