Variant X-11114923-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005333.5(HCCS):c.189C>T(p.Tyr63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,203,236 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 36 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 0 hom. 53 hem. )

Consequence

HCCS
NM_005333.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.32

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-11114923-C-T is Benign according to our data. Variant chrX-11114923-C-T is described in ClinVar as [Benign]. Clinvar id is 719798.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-11114923-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.32 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 36 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HCCS	NM_005333.5 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/7	ENST00000380762.5
HCCS	NM_001122608.3 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/7
HCCS	NM_001171991.3 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HCCS	ENST00000380762.5 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/7	1	NM_005333.5	P1
HCCS	ENST00000380763.7 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/7	1		P1
HCCS	ENST00000321143.8 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/7	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

154

AN:

112012

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

34196

show subpopulations

Gnomad AFR

AF:

0.00445

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00122

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:

0.0000376

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.000409

AC:

AN:

183422

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

67858

show subpopulations

Gnomad AFR exome

AF:

0.00463

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000489

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000183

AC:

200

AN:

1091170

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

356812

show subpopulations

Gnomad4 AFR exome

AF:

0.00403

Gnomad4 AMR exome

AF:

0.000398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000646

Gnomad4 OTH exome

AF:

0.000545

GnomAD4 genome

AF:

0.00137

AC:

154

AN:

112066

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

34260

show subpopulations

Gnomad4 AFR

AF:

0.00445

Gnomad4 AMR

AF:

0.00122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.00173

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HCCS-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.099

DANN

Benign

0.87

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