Variant X-11114909-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005333.5(HCCS):c.175C>T(p.Arg59Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000649 in 1,202,710 control chromosomes in the GnomAD database, including 1 homozygotes. There are 20 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R59S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000062 ( 1 hom. 19 hem. )

Consequence

HCCS
NM_005333.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HCCS	NM_005333.5 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/7	ENST00000380762.5
HCCS	NM_001122608.3 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/7
HCCS	NM_001171991.3 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HCCS	ENST00000380762.5 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/7	1	NM_005333.5	P1
HCCS	ENST00000380763.7 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/7	1		P1
HCCS	ENST00000321143.8 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/7	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000535

AC:

AN:

112106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34276

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000559

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.0000927

AC:

AN:

183460

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

67894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000289

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.000441

GnomAD4 exome

AF:

0.0000624

AC:

AN:

1090550

Hom.:

Cov.:

AF XY:

0.0000533

AC XY:

AN XY:

356172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.000148

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000275

Gnomad4 OTH exome

AF:

0.000545

GnomAD4 genome

AF:

0.0000892

AC:

AN:

112160

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000188

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000560

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00394

Alfa

AF:

0.0000563

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;D;D

FATHMM_MKL

Benign

0.33

M_CAP

Pathogenic

0.74

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Pathogenic

3.2

M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

N;N;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.40

MutPred

0.57

Loss of sheet (P = 0.0483);Loss of sheet (P = 0.0483);Loss of sheet (P = 0.0483);

MVP

0.80

MPC

0.54

ClinPred

0.23

GERP RS

4.2

Varity_R

0.53

gMVP

0.49

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

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