17-81665211-C-G

Variant names:

• chr17-81665211-C-G
• rs763982616
• NM_001039842.3:c.434G>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.434G>C​(p.Cys145Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. C145F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OXLD1 NM_001039842.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 0 publications found

Genes affected

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

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=0.022626936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039842.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXLD1	NM_001039842.3	MANE Select	c.434G>C	p.Cys145Ser	missense	Exon 2 of 2	NP_001034931.1	Q5BKU9
	OXLD1	NM_001304994.2		c.404G>C	p.Cys135Ser	missense	Exon 2 of 2	NP_001291923.1
	OXLD1	NM_001304995.2		c.*396G>C		3_prime_UTR	Exon 2 of 2	NP_001291924.1	I3L208

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXLD1	ENST00000374741.4	TSL:1 MANE Select	c.434G>C	p.Cys145Ser	missense	Exon 2 of 2	ENSP00000363873.3	Q5BKU9
	OXLD1	ENST00000934282.1		c.422G>C	p.Cys141Ser	missense	Exon 2 of 2	ENSP00000604341.1
	OXLD1	ENST00000571503.1	TSL:2	c.*396G>C		3_prime_UTR	Exon 2 of 2	ENSP00000466256.1	I3L208

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457680 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724794

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

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 85876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109772

Other (OTH) AF: 0.00 AC: 0 AN: 60254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.18
DANN	Benign	0.39
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.97	N
PhyloP100		-0.17
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.11
Sift	Benign	0.81	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.021
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.13
MPC		0.16
ClinPred		0.056	T
GERP RS		-4.2
Varity_R		0.076
gMVP		0.33

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

Other links and lift over

dbSNP: rs763982616; hg19: chr17-79632241;