X-11112064-G-A

Position:

• chrX-11112064-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_005333.5(HCCS):​c.4G>A​(p.Gly2Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000184 in 1,088,600 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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. G2D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: HCCS NM_005333.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-11112064-G-A is Benign according to our data. Variant chrX-11112064-G-A is described in ClinVar as [Benign]. Clinvar id is 2804780.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCCS	NM_005333.5	c.4G>A	p.Gly2Ser	missense_variant	2/7	ENST00000380762.5
HCCS	NM_001122608.3	c.4G>A	p.Gly2Ser	missense_variant	2/7
HCCS	NM_001171991.3	c.4G>A	p.Gly2Ser	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCCS	ENST00000380762.5	c.4G>A	p.Gly2Ser	missense_variant	2/7	1	NM_005333.5	P1
HCCS	ENST00000380763.7	c.4G>A	p.Gly2Ser	missense_variant	2/7	1		P1
HCCS	ENST00000321143.8	c.4G>A	p.Gly2Ser	missense_variant	2/7	2		P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1088600 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 354736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000240

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.52	.;.;T
M_CAP	Pathogenic	0.74	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.022	D;D;D
Sift4G	Benign	0.20	T;T;T
Polyphen		0.19	B;B;B
Vest4		0.48
MutPred		0.22		Loss of catalytic residue at G2 (P = 0.0025);Loss of catalytic residue at G2 (P = 0.0025);Loss of catalytic residue at G2 (P = 0.0025);
MVP		0.89
MPC		1.0
ClinPred		0.95	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.33
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-11130184;