rs10483213

chr22-41943521-G-Achr22-41943521-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024053.5(CENPM):c.402+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 1,140,410 control chromosomes in the GnomAD database, including 4,070 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 0.065 (419 hom., cov: 32)
  • Exomes 𝑓: 0.081 (3651 hom.)
• Consequence: CENPM NM_024053.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPM	NM_024053.5	c.402+89C>T		intron_variant		ENST00000215980.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPM	ENST00000215980.10	c.402+89C>T		intron_variant		1	NM_024053.5	P1

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9905 AN: 152110 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.0618

GnomAD4 exome AF: 0.0808 AC: 79863 AN: 988182 Hom.: 3651 AF XY: 0.0809 AC XY: 40257 AN XY: 497846

Gnomad4 AFR exome AF: 0.0136

Gnomad4 AMR exome AF: 0.0374

Gnomad4 ASJ exome AF: 0.0876

Gnomad4 EAS exome AF: 0.000236

Gnomad4 SAS exome AF: 0.0424

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.0908

Gnomad4 OTH exome AF: 0.0692

GnomAD4 genome AF: 0.0650 AC: 9902 AN: 152228 Hom.: 419 Cov.: 32 AF XY: 0.0639 AC XY: 4756 AN XY: 74422

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0870 Hom.: 838

Bravo AF: 0.0575

Asia WGS AF: 0.0190 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.22
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs10483213; hg19: chr22-42339525; COSMIC: COSV53245050; COSMIC: COSV53245050;