14-59480790-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144581.2(L3HYPDH):c.509-1439T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L3HYPDH	NM_144581.2	c.509-1439T>A		intron_variant		ENST00000247194.9

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.70
Dann	Benign	0.49

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;