Genetic Variant CENPM:c.310+721G>A (chr22-41944504-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024053.5(CENPM):c.310+721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 245,584 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0021 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0034 ( 0 hom. )

Consequence

CENPM
NM_024053.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.165

Publications

10 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024053.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CENPM	NM_024053.5	MANE Select	c.310+721G>A	intron	N/A	NP_076958.1
CENPM	NM_001304370.2		c.208+721G>A	intron	N/A	NP_001291299.1
CENPM	NM_001304372.2		c.293+721G>A	intron	N/A	NP_001291301.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CENPM	ENST00000215980.10	TSL:1 MANE Select	c.310+721G>A	intron	N/A	ENSP00000215980.5
CENPM	ENST00000718240.1		c.208+721G>A	intron	N/A	ENSP00000520685.1
CENPM	ENST00000402338.5	TSL:2	c.208+721G>A	intron	N/A	ENSP00000384731.1

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

315

AN:

150312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000493

Gnomad AMI

AF:

0.0398

Gnomad AMR

AF:

0.00120

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00339

Gnomad OTH

AF:

0.00338

GnomAD4 exome

AF:

0.00340

AC:

324

AN:

95192

Hom.:

AF XY:

0.00335

AC XY:

153

AN XY:

45694

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1558

American (AMR)

AF:

0.00

AC:

AN:

106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

604

East Asian (EAS)

AF:

0.00

AC:

AN:

394

South Asian (SAS)

AF:

0.00114

AC:

AN:

1748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

182

European-Non Finnish (NFE)

AF:

0.00360

AC:

315

AN:

87492

Other (OTH)

AF:

0.00227

AC:

AN:

3078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00209

AC:

315

AN:

150392

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

155

AN XY:

73292

show subpopulations

African (AFR)

AF:

0.000492

AC:

AN:

40648

American (AMR)

AF:

0.00120

AC:

AN:

15052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.000396

AC:

AN:

10106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00339

AC:

230

AN:

67916

Other (OTH)

AF:

0.00336

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000374

Hom.:

115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.6

(source)

DANN

Benign

0.81

PhyloP100

-0.17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over