rs10521250

Variant names:

• chr17-14039686-T-C
• rs10521250
• ENST00000449363.2:n.208-5270A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000449363.2(COX10-DT):​n.208-5270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 152,318 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.017 (39 hom., cov: 32)
• Consequence: COX10-DT ENST00000449363.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 0 publications found

Genes affected

COX10-DT (HGNC:38873): (COX10 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0175 (2663/152318) while in subpopulation NFE AF = 0.0258 (1754/68026). AF 95% confidence interval is 0.0248. There are 39 homozygotes in GnomAd4. There are 1319 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX10-DT	NR_049718.1	n.188-5270A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX10-DT	ENST00000449363.2	n.208-5270A>G		intron_variant	Intron 1 of 2	2
COX10-DT	ENST00000582752.7	n.213-5270A>G		intron_variant	Intron 1 of 4	3
COX10-DT	ENST00000602539.3	n.208-5270A>G		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2661 AN: 152200 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0175 AC: 2663 AN: 152318 Hom.: 39 Cov.: 32 AF XY: 0.0177 AC XY: 1319 AN XY: 74474

African (AFR) AF: 0.00442 AC: 184 AN: 41588

American (AMR) AF: 0.0100 AC: 153 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4826

European-Finnish (FIN) AF: 0.0403 AC: 427 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0258 AC: 1754 AN: 68026

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0244 Hom.: 86

Bravo AF: 0.0152

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.33
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10521250; hg19: chr17-13943003;