9-92332277-C-T

Variant names:

• chr9-92332277-C-T
• rs150818648
• NM_001012267.3:c.215C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001012267.3(CENPP):​c.215C>T​(p.Thr72Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,612,096 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (13 hom.)
• Consequence: CENPP NM_001012267.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0710
• Publications: 11 publications found

Genes affected

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004699141).
• BP6: Variant 9-92332277-C-T is Benign according to our data. Variant chr9-92332277-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3043563.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012267.3. 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
	CENPP	NM_001012267.3	MANE Select	c.215C>T	p.Thr72Met	missense	Exon 2 of 8	NP_001012267.1	Q6IPU0-1
	CENPP	NM_001286969.1		c.-47-5264C>T		intron	N/A	NP_001273898.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.215C>T	p.Thr72Met	missense	Exon 2 of 8	ENSP00000364737.3	Q6IPU0-1

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 361 AN: 152056 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00371

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00216 AC: 539 AN: 249942 AF XY: 0.00216

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.00359

Gnomad OTH exome AF: 0.00313

GnomAD4 exome AF: 0.00307 AC: 4480 AN: 1459922 Hom.: 13 Cov.: 30 AF XY: 0.00291 AC XY: 2113 AN XY: 726326

African (AFR) AF: 0.000749 AC: 25 AN: 33398

American (AMR) AF: 0.00141 AC: 63 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.000384 AC: 33 AN: 85952

European-Finnish (FIN) AF: 0.00187 AC: 100 AN: 53376

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00371 AC: 4124 AN: 1110942

Other (OTH) AF: 0.00221 AC: 133 AN: 60308

GnomAD4 genome AF: 0.00238 AC: 362 AN: 152174 Hom.: 1 Cov.: 33 AF XY: 0.00208 AC XY: 155 AN XY: 74426

African (AFR) AF: 0.00130 AC: 54 AN: 41510

American (AMR) AF: 0.000981 AC: 15 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00371 AC: 252 AN: 67990

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00294 Hom.: 3

Bravo AF: 0.00217

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00360 AC: 31

ExAC AF: 0.00250 AC: 303

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00273

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CENPP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.071
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.088
Sift	Benign	0.12	T
Sift4G	Uncertain	0.031	D
Polyphen		0.27	B
Vest4		0.22
MVP		0.15
MPC		0.52
ClinPred		0.036	T
GERP RS		-3.4
Varity_R		0.014
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs150818648; hg19: chr9-95094559; COSMIC: COSV100980993;