chr19-14564848-C-T

Variant names:

• chr19-14564848-C-T
• rs117833765
• NM_138501.6:c.552C>T

Variant summary

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

The NM_001321170.1(TECR):​c.597C>T​(p.Tyr199Tyr) 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_001321170.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.534
• Publications: 3 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), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 436973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.534 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321170.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	NM_138501.6	MANE Select	c.552C>T	p.Tyr184Tyr	synonymous	Exon 8 of 13	NP_612510.1
	TECR	NM_001321170.1		c.597C>T	p.Tyr199Tyr	synonymous	Exon 9 of 14	NP_001308099.1
	TECR	NR_038103.2		n.687C>T		non_coding_transcript_exon	Exon 8 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	ENST00000215567.10	TSL:1 MANE Select	c.552C>T	p.Tyr184Tyr	synonymous	Exon 8 of 13	ENSP00000215567.4
	TECR	ENST00000596073.6	TSL:1	c.666C>T	p.Tyr222Tyr	synonymous	Exon 7 of 12	ENSP00000472697.2
	TECR	ENST00000601187.1	TSL:3	c.122C>T	p.Thr41Ile	missense	Exon 2 of 6	ENSP00000472957.1

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

GnomAD2 exomes AF: 0.00127 AC: 320 AN: 251416 AF XY: 0.00178

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00984 AC: 849 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53346

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1112006

Other (OTH) AF: 0.000993 AC: 60 AN: 60394

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

African (AFR) AF: 0.0000963 AC: 4 AN: 41540

American (AMR) AF: 0.000262 AC: 4 AN: 15294

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

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5088

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68010

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

Alfa AF: 0.000296 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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
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
PhyloP100		0.53
Sift4G	Benign	0.93	T
MVP		0.81
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs117833765; hg19: chr19-14675660;