X-11114527-C-T

Position:

• chrX-11114527-C-T

Variant summary

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

The NM_005333.5(HCCS):​c.101-308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 112,470 control chromosomes in the GnomAD database, including 10 homozygotes. There are 292 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 0.0092 (10 hom., 292 hem., cov: 23)
• Consequence: HCCS NM_005333.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.559

Genes affected

HCCS (HGNC:4837): (holocytochrome c synthase) The protein encoded by this gene is an enzyme that covalently links a heme group to the apoprotein of cytochrome c. Defects in this gene are a cause of microphthalmia syndromic type 7 (MCOPS7). Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-11114527-C-T is Benign according to our data. Variant chrX-11114527-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1185924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00919 (1034/112470) while in subpopulation AFR AF= 0.0318 (984/30909). AF 95% confidence interval is 0.0302. There are 10 homozygotes in gnomad4. There are 292 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCCS	NM_005333.5	c.101-308C>T		intron_variant		ENST00000380762.5
HCCS	NM_001122608.3	c.101-308C>T		intron_variant
HCCS	NM_001171991.3	c.101-308C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCCS	ENST00000380762.5	c.101-308C>T		intron_variant		1	NM_005333.5	P1
HCCS	ENST00000380763.7	c.101-308C>T		intron_variant		1		P1
HCCS	ENST00000321143.8	c.101-308C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.00917 AC: 1031 AN: 112416 Hom.: 10 Cov.: 23 AF XY: 0.00836 AC XY: 289 AN XY: 34582

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00253

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000278

Gnomad SAS AF: 0.000365

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00915

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

GnomAD4 genome AF: 0.00919 AC: 1034 AN: 112470 Hom.: 10 Cov.: 23 AF XY: 0.00843 AC XY: 292 AN XY: 34646

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.00253

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000279

Gnomad4 SAS AF: 0.000366

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00904

Alfa AF: 0.00668 Hom.: 23

Bravo AF: 0.0105

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

Feb 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.58

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: rs144019232; hg19: chrX-11132647;