X-38352403-G-A

Position:

• chrX-38352403-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001407092.1(OTC):​c.-79-215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 295,497 control chromosomes in the GnomAD database, including 17 homozygotes. There are 256 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (13 hom., 210 hem., cov: 22)
  • Exomes 𝑓: 0.0012 (4 hom. 46 hem.)
• Consequence: OTC NM_001407092.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.947

Genes affected

OTC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant X-38352403-G-A is Benign according to our data. Variant chrX-38352403-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1190289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00701 (779/111206) while in subpopulation AFR AF= 0.0236 (721/30549). AF 95% confidence interval is 0.0222. There are 13 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTC	NM_001407092.1	c.-79-215G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 775 AN: 111153 Hom.: 13 Cov.: 22 AF XY: 0.00623 AC XY: 208 AN XY: 33395

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00404

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00879

GnomAD4 exome AF: 0.00117 AC: 215 AN: 184291 Hom.: 4 AF XY: 0.000829 AC XY: 46 AN XY: 55461

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000192

Gnomad4 SAS exome AF: 0.000137

Gnomad4 FIN exome AF: 0.000560

Gnomad4 NFE exome AF: 0.0000541

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00701 AC: 779 AN: 111206 Hom.: 13 Cov.: 22 AF XY: 0.00628 AC XY: 210 AN XY: 33458

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.00404

Gnomad4 ASJ AF: 0.000379

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000169

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00868

Alfa AF: 0.00712 Hom.: 24

Bravo AF: 0.00821

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs139948134; hg19: chrX-38211656;