X-11120925-A-T

Variant names:

• chrX-11120925-A-T
• NM_005333.5:c.540A>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005333.5(HCCS):​c.540A>T​(p.Pro180Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: HCCS NM_005333.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.32

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-11120925-A-T is Benign according to our data. Variant chrX-11120925-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2809609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.32 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCCS	NM_005333.5	c.540A>T	p.Pro180Pro	synonymous_variant	Exon 6 of 7	ENST00000380762.5	NP_005324.3
HCCS	NM_001122608.3	c.540A>T	p.Pro180Pro	synonymous_variant	Exon 6 of 7		NP_001116080.1
HCCS	NM_001171991.3	c.540A>T	p.Pro180Pro	synonymous_variant	Exon 6 of 7		NP_001165462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCCS	ENST00000380762.5	c.540A>T	p.Pro180Pro	synonymous_variant	Exon 6 of 7	1	NM_005333.5	ENSP00000370139.4
HCCS	ENST00000380763.7	c.540A>T	p.Pro180Pro	synonymous_variant	Exon 6 of 7	1		ENSP00000370140.3
HCCS	ENST00000321143.8	c.540A>T	p.Pro180Pro	synonymous_variant	Exon 6 of 7	2		ENSP00000326579.4
ARHGAP6	ENST00000657361.1	c.1733-880T>A		intron_variant	Intron 12 of 13			ENSP00000499351.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 06, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-11139045;