17-81666534-G-A

Variant names:

• chr17-81666534-G-A
• NM_001039842.3:c.44C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039842.3(OXLD1):​c.44C>T​(p.Ala15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,372,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: OXLD1 NM_001039842.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.831

Genes affected

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07150033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXLD1	NM_001039842.3	c.44C>T	p.Ala15Val	missense_variant	Exon 1 of 2	ENST00000374741.4	NP_001034931.1
CCDC137	NM_199287.3	c.-233G>A		upstream_gene_variant		ENST00000329214.13	NP_954981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXLD1	ENST00000374741.4	c.44C>T	p.Ala15Val	missense_variant	Exon 1 of 2	1	NM_001039842.3	ENSP00000363873.3
CCDC137	ENST00000329214.13	c.-233G>A		upstream_gene_variant		1	NM_199287.3	ENSP00000329360.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1372942 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 679438

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44C>T (p.A15V) alteration is located in exon 1 (coding exon 1) of the OXLD1 gene. This alteration results from a C to T substitution at nucleotide position 44, causing the alanine (A) at amino acid position 15 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.2
DANN	Benign	0.88
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.41	T;.
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.73	N;.
REVEL	Benign	0.015
Sift	Benign	0.31	T;.
Sift4G	Benign	0.75	T;.
Polyphen		0.020	B;.
Vest4		0.20
MutPred		0.40		Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);
MVP		0.10
MPC		0.13
ClinPred		0.053	T
GERP RS		-1.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.1
Varity_R		0.036
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79633564;