rs6002551

Positions:

• chr22-41942148-G-A

Variant summary

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

The NM_024053.5(CENPM):​c.402+1462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,122 control chromosomes in the GnomAD database, including 4,060 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 0.20 (4060 hom., cov: 32)
• Consequence: CENPM NM_024053.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPM	NM_024053.5	c.402+1462C>T		intron_variant		ENST00000215980.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPM	ENST00000215980.10	c.402+1462C>T		intron_variant		1	NM_024053.5	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30423 AN: 152004 Hom.: 4034 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 30494 AN: 152122 Hom.: 4060 Cov.: 32 AF XY: 0.203 AC XY: 15105 AN XY: 74372

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0490

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.189

Alfa AF: 0.145 Hom.: 2868

Bravo AF: 0.226

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.1
DANN	Benign	0.71

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: rs6002551; hg19: chr22-42338152;