rs3752591

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000215980.10(CENPM):​c.402+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,028,960 control chromosomes in the GnomAD database, including 27,154 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4651 hom., cov: 32)
Exomes 𝑓: 0.21 ( 22503 hom. )

Consequence

CENPM
ENST00000215980.10 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.06
Variant links:
Genes affected
CENPM (HGNC:18352): (centromere protein M) The protein encoded by this gene is an inner protein of the kinetochore, the multi-protein complex that binds spindle microtubules to regulate chromosome segregation during cell division. It belongs to the constitutive centromere-associated network protein group, whose members interact with outer kinetochore proteins and help to maintain centromere identity at each cell division cycle. The protein is structurally related to GTPases but cannot bind guanosine triphosphate. A point mutation that affects interaction with another constitutive centromere-associated network protein, CENP-I, impairs kinetochore assembly and chromosome alignment, suggesting that it is required for kinetochore formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CENPMNM_024053.5 linkuse as main transcriptc.402+98T>C intron_variant ENST00000215980.10 NP_076958.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CENPMENST00000215980.10 linkuse as main transcriptc.402+98T>C intron_variant 1 NM_024053.5 ENSP00000215980 P1Q9NSP4-1

Frequencies

GnomAD3 genomes
AF:
0.236
AC:
35819
AN:
151974
Hom.:
4630
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.277
Gnomad AMI
AF:
0.179
Gnomad AMR
AF:
0.365
Gnomad ASJ
AF:
0.264
Gnomad EAS
AF:
0.121
Gnomad SAS
AF:
0.316
Gnomad FIN
AF:
0.186
Gnomad MID
AF:
0.234
Gnomad NFE
AF:
0.191
Gnomad OTH
AF:
0.240
GnomAD4 exome
AF:
0.214
AC:
187978
AN:
876866
Hom.:
22503
AF XY:
0.216
AC XY:
95910
AN XY:
443828
show subpopulations
Gnomad4 AFR exome
AF:
0.277
Gnomad4 AMR exome
AF:
0.492
Gnomad4 ASJ exome
AF:
0.261
Gnomad4 EAS exome
AF:
0.114
Gnomad4 SAS exome
AF:
0.305
Gnomad4 FIN exome
AF:
0.192
Gnomad4 NFE exome
AF:
0.195
Gnomad4 OTH exome
AF:
0.228
GnomAD4 genome
AF:
0.236
AC:
35884
AN:
152094
Hom.:
4651
Cov.:
32
AF XY:
0.240
AC XY:
17826
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.278
Gnomad4 AMR
AF:
0.365
Gnomad4 ASJ
AF:
0.264
Gnomad4 EAS
AF:
0.120
Gnomad4 SAS
AF:
0.317
Gnomad4 FIN
AF:
0.186
Gnomad4 NFE
AF:
0.191
Gnomad4 OTH
AF:
0.237
Alfa
AF:
0.214
Hom.:
5157
Bravo
AF:
0.254
Asia WGS
AF:
0.231
AC:
802
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.13
DANN
Benign
0.17
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3752591; hg19: chr22-42339516; API