22-41944504-C-G

Variant names:

• chr22-41944504-C-G
• rs1023497
• NM_024053.5:c.310+721G>C

Variant summary

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

The NM_024053.5(CENPM):​c.310+721G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 245,138 control chromosomes in the GnomAD database, including 7,305 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 0.26 (5540 hom., cov: 30)
  • Exomes 𝑓: 0.18 (1765 hom.)
• Consequence: CENPM NM_024053.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPM	NM_024053.5	c.310+721G>C		intron_variant	Intron 4 of 5	ENST00000215980.10	NP_076958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPM	ENST00000215980.10	c.310+721G>C		intron_variant	Intron 4 of 5	1	NM_024053.5	ENSP00000215980.5

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38382 AN: 150132 Hom.: 5519 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.184 AC: 17455 AN: 94926 Hom.: 1765 AF XY: 0.184 AC XY: 8386 AN XY: 45554

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.0812

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.256 AC: 38446 AN: 150212 Hom.: 5540 Cov.: 30 AF XY: 0.258 AC XY: 18900 AN XY: 73176

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.251

Alfa AF: 0.0881 Hom.: 115

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs1023497; hg19: chr22-42340508;