rs1247471618

Variant names:

• chr10-98387269-C-A
• rs1247471618
• NM_032709.3:c.1486G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-98387269-C-A
• chr10-98387269-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032709.3(PYROXD2):​c.1486G>T​(p.Asp496Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. D496V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PYROXD2 NM_032709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 0 publications found

Genes affected

PYROXD2 (HGNC:23517): (pyridine nucleotide-disulphide oxidoreductase domain 2) Predicted to enable oxidoreductase activity. Involved in mitochondrion organization. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27400988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032709.3. 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
	PYROXD2	NM_032709.3	MANE Select	c.1486G>T	p.Asp496Tyr	missense	Exon 14 of 16	NP_116098.2	Q8N2H3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYROXD2	ENST00000370575.5	TSL:1 MANE Select	c.1486G>T	p.Asp496Tyr	missense	Exon 14 of 16	ENSP00000359607.4	Q8N2H3
	PYROXD2	ENST00000483923.5	TSL:1	n.2372G>T		non_coding_transcript_exon	Exon 13 of 15
	PYROXD2	ENST00000906254.1		c.1630G>T	p.Asp544Tyr	missense	Exon 14 of 16	ENSP00000576313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251368 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

⚠️ 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: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.094	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.052
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.094
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.93	P
Vest4		0.47
MutPred		0.41		Gain of sheet (P = 0.0166)
MVP		0.66
MPC		0.073
ClinPred		0.60	D
GERP RS		1.6
Varity_R		0.087
gMVP		0.52
Mutation Taster		=93/7	polymorphism

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: rs1247471618; hg19: chr10-100147026;