rs5758511

Variant names:

• chr22-41940168-G-A
• rs5758511
• ENST00000472374.6:c.7C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-41940168-G-A
• chr22-41940168-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000472374.6(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 ENST00000472374.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 55 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.403-972C>T		intron_variant	Intron 5 of 5	ENST00000215980.10	NP_076958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPM	ENST00000215980.10	c.403-972C>T		intron_variant	Intron 5 of 5	1	NM_024053.5	ENSP00000215980.5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32836 AN: 151786 Hom.: 4538 Cov.: 31

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

GnomAD2 exomes AF: 0.262 AC: 59958 AN: 228612 AF XY: 0.264

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 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.: 0 AF XY: 0.264 AC XY: 88791 AN XY: 335788

African (AFR) AF: 0.0599 AC: 1041 AN: 17388

American (AMR) AF: 0.178 AC: 7515 AN: 42264

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 6513 AN: 20776

East Asian (EAS) AF: 0.447 AC: 15882 AN: 35508

South Asian (SAS) AF: 0.212 AC: 14351 AN: 67554

European-Finnish (FIN) AF: 0.249 AC: 13049 AN: 52384

Middle Eastern (MID) AF: 0.213 AC: 882 AN: 4140

European-Non Finnish (NFE) AF: 0.277 AC: 95515 AN: 344670

Other (OTH) AF: 0.256 AC: 8362 AN: 32706

GnomAD4 genome AF: 0.216 AC: 32834 AN: 151902 Hom.: 4539 Cov.: 31 AF XY: 0.216 AC XY: 16004 AN XY: 74238

African (AFR) AF: 0.0594 AC: 2464 AN: 41462

American (AMR) AF: 0.205 AC: 3130 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2692 AN: 5126

South Asian (SAS) AF: 0.213 AC: 1020 AN: 4794

European-Finnish (FIN) AF: 0.255 AC: 2687 AN: 10548

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18940 AN: 67922

Other (OTH) AF: 0.205 AC: 433 AN: 2108

Alfa AF: 0.256 Hom.: 18091

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	T
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	N
PhyloP100		-0.13
Vest4		0.0070
GERP RS		0.78
PromoterAI		-0.014	Neutral
Mutation Taster		=177/23	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5758511; hg19: chr22-42336172; COSMIC: COSV53245189; COSMIC: COSV53245189;