rs62622415

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000039007.5(OTC):​c.867+35T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,180,579 control chromosomes in the GnomAD database, including 483 homozygotes. There are 11,736 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 29 hom., 738 hem., cov: 22)
Exomes 𝑓: 0.033 ( 454 hom. 10998 hem. )

Consequence

OTC
ENST00000039007.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.30
Variant links:
Genes affected
OTC (HGNC:8512): (ornithine transcarbamylase) This nuclear gene encodes a mitochondrial matrix enzyme. The encoded protein is involved in the urea cycle which functions to detoxify ammonia into urea for excretion. Mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. [provided by RefSeq, May 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
Variant X-38409060-T-G is Benign according to our data. Variant chrX-38409060-T-G is described in ClinVar as [Benign]. Clinvar id is 256372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0242 (2706/111645) while in subpopulation NFE AF= 0.0357 (1892/53042). AF 95% confidence interval is 0.0343. There are 29 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 29 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OTCNM_000531.6 linkuse as main transcriptc.867+35T>G intron_variant ENST00000039007.5 NP_000522.3
OTCNM_001407092.1 linkuse as main transcriptc.867+35T>G intron_variant NP_001394021.1
OTCXM_017029556.2 linkuse as main transcriptc.867+35T>G intron_variant XP_016885045.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OTCENST00000039007.5 linkuse as main transcriptc.867+35T>G intron_variant 1 NM_000531.6 ENSP00000039007 P1
OTCENST00000643344.1 linkuse as main transcriptc.*617+35T>G intron_variant, NMD_transcript_variant ENSP00000496606

Frequencies

GnomAD3 genomes
AF:
0.0243
AC:
2712
AN:
111591
Hom.:
29
Cov.:
22
AF XY:
0.0219
AC XY:
739
AN XY:
33769
show subpopulations
Gnomad AFR
AF:
0.00890
Gnomad AMI
AF:
0.0189
Gnomad AMR
AF:
0.0285
Gnomad ASJ
AF:
0.0227
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00267
Gnomad FIN
AF:
0.0164
Gnomad MID
AF:
0.0383
Gnomad NFE
AF:
0.0357
Gnomad OTH
AF:
0.0374
GnomAD3 exomes
AF:
0.0231
AC:
4179
AN:
181276
Hom.:
49
AF XY:
0.0224
AC XY:
1500
AN XY:
66958
show subpopulations
Gnomad AFR exome
AF:
0.00931
Gnomad AMR exome
AF:
0.0171
Gnomad ASJ exome
AF:
0.0243
Gnomad EAS exome
AF:
0.000145
Gnomad SAS exome
AF:
0.00563
Gnomad FIN exome
AF:
0.0181
Gnomad NFE exome
AF:
0.0360
Gnomad OTH exome
AF:
0.0236
GnomAD4 exome
AF:
0.0330
AC:
35242
AN:
1068934
Hom.:
454
Cov.:
27
AF XY:
0.0326
AC XY:
10998
AN XY:
337042
show subpopulations
Gnomad4 AFR exome
AF:
0.00912
Gnomad4 AMR exome
AF:
0.0192
Gnomad4 ASJ exome
AF:
0.0211
Gnomad4 EAS exome
AF:
0.0000998
Gnomad4 SAS exome
AF:
0.00636
Gnomad4 FIN exome
AF:
0.0185
Gnomad4 NFE exome
AF:
0.0383
Gnomad4 OTH exome
AF:
0.0309
GnomAD4 genome
AF:
0.0242
AC:
2706
AN:
111645
Hom.:
29
Cov.:
22
AF XY:
0.0218
AC XY:
738
AN XY:
33833
show subpopulations
Gnomad4 AFR
AF:
0.00885
Gnomad4 AMR
AF:
0.0285
Gnomad4 ASJ
AF:
0.0227
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00267
Gnomad4 FIN
AF:
0.0164
Gnomad4 NFE
AF:
0.0357
Gnomad4 OTH
AF:
0.0363
Alfa
AF:
0.0280
Hom.:
216
Bravo
AF:
0.0264

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Ornithine carbamoyltransferase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesSep 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.23
CADD
Benign
16
DANN
Benign
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62622415; hg19: chrX-38268313; API