dbSNP rs3752591: CENPM:c.402+98T>C (chr22-41943512-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024053.5(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
NM_024053.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.06

Publications

16 publications found

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]

CENPM links:

Genome browser will be placed here

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=-0.93).

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 rank	MANE	Protein	UniProt
CENPM	NM_024053.5 link	c.402+98T>C		intron_variant	Intron 5 of 5	ENST00000215980.10	NP_076958.1	Q9NSP4-1A0A024R1Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPM	ENST00000215980.10 link	c.402+98T>C		intron_variant	Intron 5 of 5	1	NM_024053.5	ENSP00000215980.5		Q9NSP4-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35819

AN:

151974

Hom.:

4630

Cov.:

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

African (AFR)

AF:

0.277

AC:

5877

AN:

21224

American (AMR)

AF:

0.492

AC:

14424

AN:

29288

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

4931

AN:

18886

East Asian (EAS)

AF:

0.114

AC:

3727

AN:

32594

South Asian (SAS)

AF:

0.305

AC:

17643

AN:

57926

European-Finnish (FIN)

AF:

0.192

AC:

8879

AN:

46240

Middle Eastern (MID)

AF:

0.259

AC:

779

AN:

3010

European-Non Finnish (NFE)

AF:

0.195

AC:

122527

AN:

627468

Other (OTH)

AF:

0.228

AC:

9191

AN:

40230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

6744

13489

20233

26978

33722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3704

7408

11112

14816

18520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.236

AC:

35884

AN:

152094

Hom.:

4651

Cov.:

AF XY:

0.240

AC XY:

17826

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.278

AC:

11513

AN:

41454

American (AMR)

AF:

0.365

AC:

5580

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

918

AN:

3472

East Asian (EAS)

AF:

0.120

AC:

621

AN:

5174

South Asian (SAS)

AF:

0.317

AC:

1530

AN:

4826

European-Finnish (FIN)

AF:

0.186

AC:

1974

AN:

10588

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.191

AC:

13016

AN:

67992

Other (OTH)

AF:

0.237

AC:

502

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1370

2740

4111

5481

6851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.218

Hom.:

6812

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

(source)

DANN

Benign

0.17

PhyloP100

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over