rs775674652

Variant names:

• chrX-101109936-C-A
• NM_001386188.2:c.529C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-101109936-C-A
• chrX-101109936-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001386188.2(CENPI):​c.529C>A​(p.Arg177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,094,313 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R177C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000082 (0 hom. 4 hem.)
• Consequence: CENPI NM_001386188.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10446465).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPI	NM_001386188.2	c.529C>A	p.Arg177Ser	missense_variant	Exon 6 of 22	ENST00000682095.1	NP_001373117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPI	ENST00000682095.1	c.529C>A	p.Arg177Ser	missense_variant	Exon 6 of 22		NM_001386188.2	ENSP00000507927.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000822 AC: 9 AN: 1094313 Hom.: 0 Cov.: 28 AF XY: 0.0000111 AC XY: 4 AN XY: 359999

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: 0.00000953

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.3
DANN	Benign	0.89
DEOGEN2	Benign	0.034	.;T;T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.52	T;.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.65	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.81	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.33
MutPred		0.54		Loss of methylation at K178 (P = 0.0613);Loss of methylation at K178 (P = 0.0613);Loss of methylation at K178 (P = 0.0613);
MVP		0.22
MPC		0.42
ClinPred		0.13	T
GERP RS		1.5
Varity_R		0.12
gMVP		0.070

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-100364925;