22-41944504-C-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -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
NM_024053.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.165
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 was made for transcript
Our verdict: Benign. The variant received -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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CENPM | NM_024053.5 | c.310+721G>C | intron_variant | Intron 4 of 5 | ENST00000215980.10 | NP_076958.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.256 AC: 38382AN: 150132Hom.: 5519 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
38382
AN:
150132
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.184 AC: 17455AN: 94926Hom.: 1765 AF XY: 0.184 AC XY: 8386AN XY: 45554 show subpopulations
GnomAD4 exome
AF:
AC:
17455
AN:
94926
Hom.:
AF XY:
AC XY:
8386
AN XY:
45554
Gnomad4 AFR exome
AF:
AC:
542
AN:
1548
Gnomad4 AMR exome
AF:
AC:
43
AN:
106
Gnomad4 ASJ exome
AF:
AC:
149
AN:
604
Gnomad4 EAS exome
AF:
AC:
32
AN:
394
Gnomad4 SAS exome
AF:
AC:
535
AN:
1738
Gnomad4 FIN exome
AF:
AC:
7
AN:
30
Gnomad4 NFE exome
AF:
AC:
15450
AN:
87256
Gnomad4 Remaining exome
AF:
AC:
659
AN:
3068
Heterozygous variant carriers
0
707
1415
2122
2830
3537
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
750
1500
2250
3000
3750
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome AF: 0.256 AC: 38446AN: 150212Hom.: 5540 Cov.: 30 AF XY: 0.258 AC XY: 18900AN XY: 73176 show subpopulations
GnomAD4 genome
AF:
AC:
38446
AN:
150212
Hom.:
Cov.:
30
AF XY:
AC XY:
18900
AN XY:
73176
Gnomad4 AFR
AF:
AC:
0.352919
AN:
0.352919
Gnomad4 AMR
AF:
AC:
0.371219
AN:
0.371219
Gnomad4 ASJ
AF:
AC:
0.263993
AN:
0.263993
Gnomad4 EAS
AF:
AC:
0.119658
AN:
0.119658
Gnomad4 SAS
AF:
AC:
0.317191
AN:
0.317191
Gnomad4 FIN
AF:
AC:
0.177969
AN:
0.177969
Gnomad4 NFE
AF:
AC:
0.190944
AN:
0.190944
Gnomad4 OTH
AF:
AC:
0.251442
AN:
0.251442
Heterozygous variant carriers
0
1283
2566
3850
5133
6416
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
402
804
1206
1608
2010
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism (auto)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at