rs758644053

Variant names:

• chrX-11121012-GTGT-G
• rs758644053
• NM_005333.5:c.608+24_608+26delGTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005333.5(HCCS):​c.608+24_608+26delGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,149,395 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000068 (0 hom. 3 hem.)
• Consequence: HCCS NM_005333.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.366
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant X-11121012-GTGT-G is Benign according to our data. Variant chrX-11121012-GTGT-G is described in ClinVar as Benign. ClinVar VariationId is 2889194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCCS	NM_005333.5	MANE Select	c.608+24_608+26delGTT		intron	N/A	NP_005324.3	P53701
	HCCS	NM_001122608.3		c.608+24_608+26delGTT		intron	N/A	NP_001116080.1	P53701
	HCCS	NM_001171991.3		c.608+24_608+26delGTT		intron	N/A	NP_001165462.1	P53701

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCCS	ENST00000380762.5	TSL:1 MANE Select	c.608+20_608+22delTGT		intron	N/A	ENSP00000370139.4	P53701
	HCCS	ENST00000380763.7	TSL:1	c.608+20_608+22delTGT		intron	N/A	ENSP00000370140.3	P53701
	ARHGAP6	ENST00000657361.1		c.1733-970_1733-968delACA		intron	N/A	ENSP00000499351.1	B4DN07

Frequencies

GnomAD3 genomes AF: 0.0000445 AC: 5 AN: 112362 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000374

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183457 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000675 AC: 7 AN: 1036981 Hom.: 0 AF XY: 0.00000966 AC XY: 3 AN XY: 310399

African (AFR) AF: 0.00 AC: 0 AN: 25263

American (AMR) AF: 0.000199 AC: 7 AN: 35151

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18989

East Asian (EAS) AF: 0.00 AC: 0 AN: 29980

South Asian (SAS) AF: 0.00 AC: 0 AN: 52751

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3973

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 786269

Other (OTH) AF: 0.00 AC: 0 AN: 44109

GnomAD4 genome AF: 0.0000445 AC: 5 AN: 112414 Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1 AN XY: 34574

African (AFR) AF: 0.0000323 AC: 1 AN: 30966

American (AMR) AF: 0.000374 AC: 4 AN: 10694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.00 AC: 0 AN: 2727

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6153

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53246

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs758644053; hg19: chrX-11139132;