rs1262129

Positions:

• chr14-59480790-A-C
• chr14-59480790-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
L3HYPDH	NM_144581.2	c.509-1439T>G		intron_variant		ENST00000247194.9	NP_653182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3HYPDH	ENST00000247194.9	c.509-1439T>G		intron_variant		1	NM_144581.2	ENSP00000247194	P1
L3HYPDH	ENST00000481608.1	c.-5-1439T>G		intron_variant		2		ENSP00000423874
L3HYPDH	ENST00000487285.5	c.-5-1439T>G		intron_variant		3		ENSP00000431608
L3HYPDH	ENST00000527981.1	n.730-1439T>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.538

Alfa AF: 0.448 Hom.: 6287

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1262129; hg19: chr14-59947508;