Variant X-11120047-T-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.522-860T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 323,350 control chromosomes in the GnomAD database, including 2 homozygotes. There are 183 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 0.0016 ( 1 hom., 71 hem., cov: 23)

Exomes 𝑓: 0.0015 ( 1 hom. 112 hem. )

Consequence

HCCS
NM_005333.5 intron

Scores

Splicing: ADA: 0.0002072

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.857

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:

ARHGAP6 (HGNC:676): (Rho GTPase activating protein 6) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of actin polymerization at the plasma membrane during several cellular processes. This protein is thought to have two independent functions, one as a GTPase-activating protein with specificity for RhoA, and another as a cytoskeletal protein that promotes actin remodeling. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ARHGAP6 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=-0.77).

BP6

Variant X-11120047-T-C is Benign according to our data. Variant chrX-11120047-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2659981.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 71 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HCCS	NM_005333.5 linkuse as main transcript	c.522-860T>C	intron_variant	ENST00000380762.5	NP_005324.3
HCCS	NM_001122608.3 linkuse as main transcript	c.522-860T>C	intron_variant		NP_001116080.1
HCCS	NM_001171991.3 linkuse as main transcript	c.522-860T>C	intron_variant		NP_001165462.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
HCCS	ENST00000380762.5 linkuse as main transcript	c.522-860T>C	intron_variant	1	NM_005333.5	ENSP00000370139	P1
HCCS	ENST00000380763.7 linkuse as main transcript	c.522-860T>C	intron_variant	1		ENSP00000370140	P1
ARHGAP6	ENST00000657361.1 linkuse as main transcript	c.1733-2A>G	splice_acceptor_variant			ENSP00000499351	A2
HCCS	ENST00000321143.8 linkuse as main transcript	c.522-860T>C	intron_variant	2		ENSP00000326579	P1

Frequencies

GnomAD3 genomes

AF:

0.00164

AC:

184

AN:

112254

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

AN XY:

34414

show subpopulations

Gnomad AFR

AF:

0.000324

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.00188

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00736

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.00114

AC:

AN:

83168

Hom.:

AF XY:

0.00103

AC XY:

AN XY:

26292

show subpopulations

Gnomad AFR exome

AF:

0.000449

Gnomad AMR exome

AF:

0.000594

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00716

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.00267

GnomAD4 exome

AF:

0.00152

AC:

320

AN:

211041

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

112

AN XY:

81069

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000690

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000592

Gnomad4 FIN exome

AF:

0.00667

Gnomad4 NFE exome

AF:

0.00189

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00164

AC:

184

AN:

112309

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

AN XY:

34479

show subpopulations

Gnomad4 AFR

AF:

0.000323

Gnomad4 AMR

AF:

0.00188

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00736

Gnomad4 NFE

AF:

0.00197

Gnomad4 OTH

AF:

0.00195

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00115

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

Mar 01, 2023

ARHGAP6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

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