chr14-59480790-A-C

Variant names:

• chr14-59480790-A-C
• rs1262129
• NM_144581.2:c.509-1439T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144581.2(L3HYPDH):​c.509-1439T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,084 control chromosomes in the GnomAD database, including 24,604 homozygotes. 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: 𝑓 0.54 (24604 hom., cov: 33)
• Consequence: L3HYPDH NM_144581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 publications found

Genes affected

L3HYPDH (HGNC:20488): (trans-L-3-hydroxyproline dehydratase) The protein encoded by this gene is a dehydratase that converts trans-3-hydroxy-L-proline to delta(1)-pyrroline-2-carboxylate. This enzyme may function to degrade dietary proteins that contain trans-3-hydroxy-L-proline as well as other proteins such as collagen IV. The encoded protein can be converted to an epimerase by changing a threonine to a cysteine at a catalytic site. [provided by RefSeq, Sep 2016]

ENSG00000258782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3HYPDH	NM_144581.2	c.509-1439T>G		intron_variant	Intron 1 of 4	ENST00000247194.9	NP_653182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3HYPDH	ENST00000247194.9	c.509-1439T>G		intron_variant	Intron 1 of 4	1	NM_144581.2	ENSP00000247194.4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82183 AN: 151964 Hom.: 24554 Cov.: 33

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82295 AN: 152084 Hom.: 24604 Cov.: 33 AF XY: 0.531 AC XY: 39496 AN XY: 74324

African (AFR) AF: 0.803 AC: 33299 AN: 41472

American (AMR) AF: 0.517 AC: 7907 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3472

East Asian (EAS) AF: 0.205 AC: 1061 AN: 5184

South Asian (SAS) AF: 0.478 AC: 2309 AN: 4826

European-Finnish (FIN) AF: 0.330 AC: 3478 AN: 10554

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30254 AN: 67966

Other (OTH) AF: 0.538 AC: 1138 AN: 2116

Alfa AF: 0.454 Hom.: 7415

Bravo AF: 0.566

Asia WGS AF: 0.369 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.67
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1262129; hg19: chr14-59947508;