chrX-101109555-C-T

Variant names:

• chrX-101109555-C-T
• rs201645922
• NM_001386188.2:c.447C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001386188.2(CENPI):​c.447C>T​(p.Ser149Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,206,829 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000041 (0 hom. 28 hem.)
• Consequence: CENPI NM_001386188.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0450
• Publications: 0 publications found

Genes affected

CENPI (HGNC:3968): (centromere protein I) This gene encodes a centromere protein that is a component of the CENPA-NAC (nucleosome-associated) complex. This complex is critical for accurate chromosome alignment and segregation and it ensures proper mitotic progression. This protein regulates the recruitment of kinetochore-associated proteins that are required to generate the spindle checkpoint signal. The product of this gene is involved in the response of gonadal tissues to follicle-stimulating hormone. Mutations in this gene may be involved in human X-linked disorders of gonadal development and gametogenesis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 13. [provided by RefSeq, Jan 2016]

CENPI Gene-Disease associations (from GenCC):

• idiopathic steroid-sensitive nephrotic syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant X-101109555-C-T is Benign according to our data. Variant chrX-101109555-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661051.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.045 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 28 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386188.2. 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
	CENPI	NM_001386188.2	MANE Select	c.447C>T	p.Ser149Ser	synonymous	Exon 5 of 22	NP_001373117.1	Q92674-1
	CENPI	NM_006733.3		c.447C>T	p.Ser149Ser	synonymous	Exon 4 of 21	NP_006724.2	Q92674-1
	CENPI	NM_001318521.2		c.447C>T	p.Ser149Ser	synonymous	Exon 5 of 21	NP_001305450.1	A0A8C8KX99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPI	ENST00000682095.1	MANE Select	c.447C>T	p.Ser149Ser	synonymous	Exon 5 of 22	ENSP00000507927.1	Q92674-1
	CENPI	ENST00000372927.5	TSL:5	c.447C>T	p.Ser149Ser	synonymous	Exon 4 of 21	ENSP00000362018.1	Q92674-1
	CENPI	ENST00000684367.1		c.447C>T	p.Ser149Ser	synonymous	Exon 6 of 23	ENSP00000507595.1	Q92674-1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112341 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000362

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000983 AC: 18 AN: 183139 AF XY: 0.000178

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.0000411 AC: 45 AN: 1094433 Hom.: 0 Cov.: 28 AF XY: 0.0000778 AC XY: 28 AN XY: 359837

African (AFR) AF: 0.00 AC: 0 AN: 26332

American (AMR) AF: 0.00 AC: 0 AN: 35180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19350

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.000555 AC: 30 AN: 54016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40522

Middle Eastern (MID) AF: 0.00170 AC: 7 AN: 4120

European-Non Finnish (NFE) AF: 0.00000596 AC: 5 AN: 838746

Other (OTH) AF: 0.0000652 AC: 3 AN: 45980

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112396 Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1 AN XY: 34566

African (AFR) AF: 0.00 AC: 0 AN: 31048

American (AMR) AF: 0.00 AC: 0 AN: 10566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3593

South Asian (SAS) AF: 0.000363 AC: 1 AN: 2758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6080

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53278

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.000391 Hom.: 4

Bravo AF: 0.0000189

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.3
DANN	Benign	0.66
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201645922; hg19: chrX-100364544;