17-81666540-A-G

Variant names:

• chr17-81666540-A-G
• rs2036627271
• NM_001039842.3:c.38T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039842.3(OXLD1):​c.38T>C​(p.Val13Ala) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V13E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OXLD1 NM_001039842.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042500764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXLD1	NM_001039842.3	c.38T>C	p.Val13Ala	missense_variant	Exon 1 of 2	ENST00000374741.4	NP_001034931.1
CCDC137	NM_199287.3	c.-227A>G		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.38T>C	p.Val13Ala	missense_variant	Exon 1 of 2	1	NM_001039842.3	ENSP00000363873.3
CCDC137	ENST00000329214.13	c.-227A>G		upstream_gene_variant		1	NM_199287.3	ENSP00000329360.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1368104 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 676980

African (AFR) AF: 0.00 AC: 0 AN: 28402

American (AMR) AF: 0.00 AC: 0 AN: 34772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23744

East Asian (EAS) AF: 0.00 AC: 0 AN: 32358

South Asian (SAS) AF: 0.00 AC: 0 AN: 77508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074404

Other (OTH) AF: 0.00 AC: 0 AN: 56656

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.2
DANN	Benign	0.35
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.21	T;.
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N;.
PhyloP100		-0.98
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.38	N;.
REVEL	Benign	0.010
Sift	Benign	1.0	T;.
Sift4G	Benign	0.86	T;.
Polyphen		0.0010	B;.
Vest4		0.14
MVP		0.12
MPC		0.16
ClinPred		0.041	T
GERP RS		-1.9
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.019
gMVP		0.11

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: rs2036627271; hg19: chr17-79633570;