Variant X-11114824-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005333.5(HCCS):c.101-11G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,204,230 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 83 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 0.00017 ( 0 hom., 5 hem., cov: 24)

Exomes 𝑓: 0.00019 ( 0 hom. 78 hem. )

Consequence

HCCS
NM_005333.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004864

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.950

Variant links:

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]

HCCS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant X-11114824-G-C is Benign according to our data. Variant chrX-11114824-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2659980.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HCCS	NM_005333.5 linkuse as main transcript	c.101-11G>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000380762.5
HCCS	NM_001122608.3 linkuse as main transcript	c.101-11G>C	splice_polypyrimidine_tract_variant, intron_variant
HCCS	NM_001171991.3 linkuse as main transcript	c.101-11G>C	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
HCCS	ENST00000380762.5 linkuse as main transcript	c.101-11G>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_005333.5	P1
HCCS	ENST00000380763.7 linkuse as main transcript	c.101-11G>C	splice_polypyrimidine_tract_variant, intron_variant	1		P1
HCCS	ENST00000321143.8 linkuse as main transcript	c.101-11G>C	splice_polypyrimidine_tract_variant, intron_variant	2		P1

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111771

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

33945

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000755

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000226

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000191

AC:

AN:

182903

Hom.:

AF XY:

0.000223

AC XY:

AN XY:

67397

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.000938

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000193

AC:

211

AN:

1092406

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

AN XY:

358054

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000826

Gnomad4 EAS exome

AF:

0.00328

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.0000654

GnomAD4 genome

AF:

0.000170

AC:

AN:

111824

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

34008

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000755

Gnomad4 EAS

AF:

0.00141

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000155

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

HCCS: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.3

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.0

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over