Genetic Variant OXLD1:p.Val13Glu (chr17-81666540-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039842.3(OXLD1):c.38T>A(p.Val13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,520,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

OXLD1
NM_001039842.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.977

Publications

0 publications found

Variant links:

Genes affected

OXLD1 (HGNC:27901): (oxidoreductase like domain containing 1)

OXLD1 links:

CCDC137 (HGNC:33451): (coiled-coil domain containing 137) Enables RNA binding activity. Located in chromosome and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

CCDC137 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.104225785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXLD1	NM_001039842.3 link	c.38T>A	p.Val13Glu	missense_variant	Exon 1 of 2	ENST00000374741.4	NP_001034931.1	Q5BKU9
CCDC137	NM_199287.3 link	c.-227A>T		upstream_gene_variant		ENST00000329214.13	NP_954981.1	Q6PK04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXLD1	ENST00000374741.4 link	c.38T>A	p.Val13Glu	missense_variant	Exon 1 of 2	1	NM_001039842.3	ENSP00000363873.3		Q5BKU9
CCDC137	ENST00000329214.13 link	c.-227A>T		upstream_gene_variant		1	NM_199287.3	ENSP00000329360.8		Q6PK04

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.31e-7

AC:

AN:

1368104

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28402

American (AMR)

AF:

0.00

AC:

AN:

34772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23744

East Asian (EAS)

AF:

0.00

AC:

AN:

32358

South Asian (SAS)

AF:

0.00

AC:

AN:

77508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074404

Other (OTH)

AF:

0.0000177

AC:

AN:

56656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 09, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.38T>A (p.V13E) alteration is located in exon 1 (coding exon 1) of the OXLD1 gene. This alteration results from a T to A substitution at nucleotide position 38, causing the valine (V) at amino acid position 13 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.26

T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.

PhyloP100

-0.98

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.075

Sift

Benign

0.24

T;.

Sift4G

Benign

0.23

T;.

Polyphen

0.58

P;.

Vest4

0.48

MutPred

0.37

Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);

MVP

0.24

MPC

0.21

ClinPred

0.33

GERP RS

-1.9

PromoterAI

0.35

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.11

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-81666540-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over