X-11118170-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005333.5(HCCS):c.402-331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 112,359 control chromosomes in the GnomAD database, including 43 homozygotes. There are 470 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.016 (43 hom., 470 hem., cov: 23)
• Consequence: HCCS NM_005333.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-11118170-A-G is Benign according to our data. Variant chrX-11118170-A-G is described in ClinVar as [Benign]. Clinvar id is 1234098.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCCS	NM_005333.5	c.402-331A>G		intron_variant		ENST00000380762.5
HCCS	NM_001122608.3	c.402-331A>G		intron_variant
HCCS	NM_001171991.3	c.402-331A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCCS	ENST00000380762.5	c.402-331A>G		intron_variant		1	NM_005333.5	P1
HCCS	ENST00000380763.7	c.402-331A>G		intron_variant		1		P1
ARHGAP6	ENST00000657361.1	c.*158T>C		3_prime_UTR_variant	14/14			A2
HCCS	ENST00000321143.8	c.402-331A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 1797 AN: 112303 Hom.: 43 Cov.: 23 AF XY: 0.0136 AC XY: 469 AN XY: 34451

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00996

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000281

Gnomad OTH AF: 0.0145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0160 AC: 1801 AN: 112359 Hom.: 43 Cov.: 23 AF XY: 0.0136 AC XY: 470 AN XY: 34517

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.00995

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000281

Gnomad4 OTH AF: 0.0143

Alfa AF: 0.00706 Hom.: 42

Bravo AF: 0.0187

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

GeneDx

Apr 09, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.2
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs7885793; hg19: chrX-11136290;