chrX-11118547-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_005333.5(HCCS):c.448A>G(p.Ile150Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,184,523 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 65 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00015 ( 0 hom. 62 hem. )

Consequence

HCCS
NM_005333.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.72

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant X-11118547-A-G is Benign according to our data. Variant chrX-11118547-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1740941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005333.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HCCS	NM_005333.5	MANE Select	c.448A>G	p.Ile150Val	missense	Exon 5 of 7	NP_005324.3	P53701
HCCS	NM_001122608.3		c.448A>G	p.Ile150Val	missense	Exon 5 of 7	NP_001116080.1	P53701
HCCS	NM_001171991.3		c.448A>G	p.Ile150Val	missense	Exon 5 of 7	NP_001165462.1	P53701

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HCCS	ENST00000380762.5	TSL:1 MANE Select	c.448A>G	p.Ile150Val	missense	Exon 5 of 7	ENSP00000370139.4	P53701
HCCS	ENST00000380763.7	TSL:1	c.448A>G	p.Ile150Val	missense	Exon 5 of 7	ENSP00000370140.3	P53701
HCCS	ENST00000321143.8	TSL:2	c.448A>G	p.Ile150Val	missense	Exon 5 of 7	ENSP00000326579.4	P53701

Frequencies

GnomAD3 genomes

AF:

0.0000981

AC:

AN:

112145

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000218

AC:

AN:

183453

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000488

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000149

AC:

160

AN:

1072378

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

AN XY:

339648

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25924

American (AMR)

AF:

0.00

AC:

AN:

35191

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19230

East Asian (EAS)

AF:

0.00

AC:

AN:

30100

South Asian (SAS)

AF:

0.00

AC:

AN:

53521

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4070

European-Non Finnish (NFE)

AF:

0.000182

AC:

149

AN:

818591

Other (OTH)

AF:

0.000243

AC:

AN:

45233

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000981

AC:

AN:

112145

Hom.:

Cov.:

AF XY:

0.0000875

AC XY:

AN XY:

34295

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30876

American (AMR)

AF:

0.00

AC:

AN:

10567

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3592

South Asian (SAS)

AF:

0.00

AC:

AN:

2704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000207

AC:

AN:

53263

Other (OTH)

AF:

0.00

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.3

PhyloP100

8.7

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.97

REVEL

Uncertain

0.46

Sift

Benign

0.23

Sift4G

Benign

0.31

Polyphen

1.0

Vest4

0.42

MutPred

0.53

Gain of MoRF binding (P = 0.1235)

MVP

0.84

MPC

1.1

ClinPred

0.84

GERP RS

4.4

Varity_R

0.42

gMVP

0.74

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over