chr19-14529591-C-T

Variant names:

• chr19-14529591-C-T
• rs45556632
• NM_001321170.1:c.-128C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321170.1(TECR):​c.-128C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,410,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TECR NM_001321170.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 4 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]

DNAJB1 (HGNC:5270): (DnaJ heat shock protein family (Hsp40) member B1) This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

MIR639 (HGNC:32895): (microRNA 639) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	NM_001321170.1		c.-128C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001308099.1	Q9NZ01
	TECR	NM_001321170.1		c.-128C>T		5_prime_UTR	Exon 1 of 14	NP_001308099.1	Q9NZ01
	MIR639	NR_030369.1		n.49C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECR	ENST00000882752.1		c.-106C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000552811.1
	TECR	ENST00000913609.1		c.-106C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000583668.1
	TECR	ENST00000913612.1		c.-106C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000583671.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000819 AC: 2 AN: 244156 AF XY: 0.00000750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1410684 Hom.: 0 Cov.: 25 AF XY: 0.00000426 AC XY: 3 AN XY: 704564

African (AFR) AF: 0.00 AC: 0 AN: 32442

American (AMR) AF: 0.00 AC: 0 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.0000470 AC: 4 AN: 85144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4946

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067432

Other (OTH) AF: 0.00 AC: 0 AN: 58484

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.8
DANN	Benign	0.95
PhyloP100		-0.010
PromoterAI		0.013	Neutral

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: rs45556632; hg19: chr19-14640403;