22-41944504-C-G

Variant summary

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

The NM_024053.5(CENPM):​c.310+721G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 245,138 control chromosomes in the GnomAD database, including 7,305 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 0.26 ( 5540 hom., cov: 30)
Exomes 𝑓: 0.18 ( 1765 hom. )

Consequence

CENPM
NM_024053.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.165
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CENPMNM_024053.5 linkuse as main transcriptc.310+721G>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.310+721G>C intron_variant 1 NM_024053.5 ENSP00000215980 P1Q9NSP4-1

Frequencies

GnomAD3 genomes
AF:
0.256
AC:
38382
AN:
150132
Hom.:
5519
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.352
Gnomad AMI
AF:
0.174
Gnomad AMR
AF:
0.371
Gnomad ASJ
AF:
0.264
Gnomad EAS
AF:
0.120
Gnomad SAS
AF:
0.316
Gnomad FIN
AF:
0.178
Gnomad MID
AF:
0.250
Gnomad NFE
AF:
0.191
Gnomad OTH
AF:
0.254
GnomAD4 exome
AF:
0.184
AC:
17455
AN:
94926
Hom.:
1765
AF XY:
0.184
AC XY:
8386
AN XY:
45554
show subpopulations
Gnomad4 AFR exome
AF:
0.350
Gnomad4 AMR exome
AF:
0.406
Gnomad4 ASJ exome
AF:
0.247
Gnomad4 EAS exome
AF:
0.0812
Gnomad4 SAS exome
AF:
0.308
Gnomad4 FIN exome
AF:
0.233
Gnomad4 NFE exome
AF:
0.177
Gnomad4 OTH exome
AF:
0.215
GnomAD4 genome
AF:
0.256
AC:
38446
AN:
150212
Hom.:
5540
Cov.:
30
AF XY:
0.258
AC XY:
18900
AN XY:
73176
show subpopulations
Gnomad4 AFR
AF:
0.353
Gnomad4 AMR
AF:
0.371
Gnomad4 ASJ
AF:
0.264
Gnomad4 EAS
AF:
0.120
Gnomad4 SAS
AF:
0.317
Gnomad4 FIN
AF:
0.178
Gnomad4 NFE
AF:
0.191
Gnomad4 OTH
AF:
0.251
Alfa
AF:
0.0881
Hom.:
115
Bravo
AF:
0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
4.0
DANN
Benign
0.74

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

LitVar

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

Other links and lift over

dbSNP: rs1023497; hg19: chr22-42340508; API