dbSNP rs5758511: CENPM:p.Arg3* (chr22-41940168-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001110215.3(CENPM):c.7C>T(p.Arg3*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 769,292 control chromosomes in the GnomAD database, including 27,734 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 0.22 ( 4539 hom., cov: 31)

Exomes 𝑓: 0.26 ( 23195 hom. )

Consequence

CENPM
NM_001110215.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPM	NM_024053.5 link	c.403-972C>T		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.403-972C>T		intron_variant	Intron 5 of 5	1	NM_024053.5	ENSP00000215980.5		Q9NSP4-1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32836

AN:

151786

Hom.:

4538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.206

GnomAD3 exomes

AF:

0.262

AC:

59958

AN:

228612

Hom.:

9031

AF XY:

0.264

AC XY:

32837

AN XY:

124336

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.555

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.264

AC:

163110

AN:

617390

Hom.:

23195

Cov.:

AF XY:

0.264

AC XY:

88791

AN XY:

335788

show subpopulations

Gnomad4 AFR exome

AF:

0.0599

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.447

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.216

AC:

32834

AN:

151902

Hom.:

4539

Cov.:

AF XY:

0.216

AC XY:

16004

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.0594

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.265

Hom.:

12238

Bravo

AF:

0.207

TwinsUK

AF:

0.270

AC:

1001

ALSPAC

AF:

0.280

AC:

1080

ESP6500AA

AF:

0.0580

AC:

182

ESP6500EA

AF:

0.282

AC:

2020

ExAC

AF:

0.250

AC:

30121

Asia WGS

AF:

0.307

AC:

1072

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.9

DANN

Uncertain

0.98

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.061

Vest4

0.0070

GERP RS

0.78

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over